{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117847","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36080225","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85137579924&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=391803","label":"url"}],"paper_title":{"en":"Betuletol, a propolis component, suppresses IL-33 gene expression and effective against eosinophilia","ja":"Betuletol, a propolis component, suppresses IL-33 gene expression and effective against eosinophilia"},"authors":{"en":[{"name":"Aurpita Shaha"},{"name":"Rezwanul Islam"},{"name":"Tanaka Naonobu"},{"name":"Kashiwada Yoshiki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"},{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"}],"ja":[{"name":"Aurpita Shaha"},{"name":"Rezwanul Islam"},{"name":"田中 直伸"},{"name":"柏田 良樹"},{"name":"福井 裕行"},{"name":"武田 憲昭"},{"name":"北村 嘉章"},{"name":"水口 博之"}]},"description":{"en":"Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations.","ja":"Propolis, a resinous substance produced by honeybees, has been used in folk medicine since ancient times due to its many biological benefits such as antitumor, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory effects. Propolis contains flavonoids, terpenoids, aromatic aldehydes, and alcohols, which vary with different climate and environmental conditions. In our study, we examined the antiallergic activity of Brazilian green propolis (BGP) and isolated the active compound that can suppress an allergy-sensitive gene, IL-33, expression and eosinophilia. Ethanolic extract of BGP freeze-dried powder was fractionated with several solvent systems, and the active fractions were collected based on activity measurement. The single active compound was found by thin-layer chromatography. Using column chromatography and NMR, the active compound was isolated and identified as 3,5,7-trihydroxy-6,4'-dimethoxyflavone, also known as betuletol. Further, the antiallergic activity of that has been examined in PMA-induced up-regulation of IL-33 gene expression in Swiss 3T3 cells. Our data showed the IL-33 gene suppression both by BGP and the isolated active compound, betuletol. We also found that betuletol suppressed ERK phosphorylation, suggesting it could be effective in suppressing IL-33 mediated eosinophilic chronic inflammation and will provide new insights to develop potent therapeutics against allergic inflammations."},"publication_date":"2022-08-25","publication_name":{"en":"Molecules","ja":"Molecules"},"volume":"Vol.27","number":"No.17","starting_page":"5459","ending_page":"5459","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/molecules27175459"],"issn":["1420-3049"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/116050","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33614927","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=385391","label":"url"}],"paper_title":{"en":"Effects of narrow-band UVB on nasal symptom and upregulation of histamine H1 receptor mRNA in allergic rhinitis model rats","ja":"Effects of narrow-band UVB on nasal symptom and upregulation of histamine H1 receptor mRNA in allergic rhinitis model rats"},"authors":{"en":[{"name":"Kamimura Seiichiro"},{"name":"Kitamura Yoshiaki"},{"name":"Fujii Tatsuya"},{"name":"Okamoto Kentaro"},{"name":"Sanada Nanae"},{"name":"Okajima Natsuki"},{"name":"Wakugawa Tomoharu"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"神村 盛一郎"},{"name":"北村 嘉章"},{"name":"藤井 達也"},{"name":"Okamoto Kentaro"},{"name":"Sanada Nanae"},{"name":"Okajima Natsuki"},{"name":"Wakugawa Tomoharu"},{"name":"福井 裕行"},{"name":"水口 博之"},{"name":"武田 憲昭"}]},"description":{"en":"NA.","ja":"Intranasal pre-irradiation with narrow-band UVB dose-dependently inhibited sneezes and upregulation of H1R gene expression of the nasal mucosa in AR model rats, suggesting that the inhibition of nasal upregulation of H1R gene expression suppressed nasal symptom. The suppression after narrow-band UVB irradiation at a dose of 600 mJ/cm"},"publication_date":"2021-01-08","publication_name":{"en":"Laryngoscope Investigative Otolaryngology","ja":"Laryngoscope Investigative Otolaryngology"},"volume":"Vol.6","number":"No.1","starting_page":"34","ending_page":"41","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/lio2.518"],"issn":["2378-8038"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=375741","label":"url"}],"paper_title":{"en":"レンコンエキスパウダー摂取による鼻と眼のアレルギー症状軽減効果の検証―プラセボ対照ランダム化二重盲検並行群間比較試験―","ja":"レンコンエキスパウダー摂取による鼻と眼のアレルギー症状軽減効果の検証―プラセボ対照ランダム化二重盲検並行群間比較試験―"},"authors":{"en":[{"name":"永峰 賢一"},{"name":"竹内 心"},{"name":"中川 秀紀"},{"name":"海老原 淑子"},{"name":"Wakugawa Tomoharu"},{"name":"Kitamura Yoshiaki"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"永峰 賢一"},{"name":"竹内 心"},{"name":"中川 秀紀"},{"name":"海老原 淑子"},{"name":"湧川 朝治"},{"name":"北村 嘉章"},{"name":"福井 裕行"},{"name":"水口 博之"},{"name":"武田 憲昭"}]},"publication_date":"2020-09","publication_name":{"en":"Japanese Pharmacology & Therapeutics","ja":"薬理と治療"},"volume":"Vol.48","number":"No.9","starting_page":"1559","ending_page":"1569","languages":["jpn"],"referee":true,"identifiers":{"issn":["0386-3603"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=375636","label":"url"}],"paper_title":{"en":"Identification and characterization of the anti-allergic compound from lotus root.","ja":"Identification and characterization of the anti-allergic compound from lotus root."},"authors":{"en":[{"name":"Tomoharu Wakugawa"},{"name":"Kenichi Nagamine"},{"name":"Miharu Hiramatsu"},{"name":"Mayuko Takeda"},{"name":"Chika Kawata"},{"name":"Yoshiki Kashiwada"},{"name":"Keiko Shinohara"},{"name":"Eiji Sawada"},{"name":"Masami Yabumoto"},{"name":"Fujino Hiromichi"},{"name":"Kitamura Yoshiaki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"},{"name":"Mizuguchi Hiroyuki"}],"ja":[{"name":"湧川 朝治"},{"name":"Kenichi Nagamine"},{"name":"Miharu Hiramatsu"},{"name":"Mayuko Takeda"},{"name":"Chika Kawata"},{"name":"Yoshiki Kashiwada"},{"name":"Keiko Shinohara"},{"name":"Eiji Sawada"},{"name":"Masami Yabumoto"},{"name":"藤野 裕道"},{"name":"北村 嘉章"},{"name":"福井 裕行"},{"name":"武田 憲昭"},{"name":"水口 博之"}]},"publication_date":"2020-08","publication_name":{"en":"Traditional & Kampo Medicine","ja":"Traditional & Kampo Medicine"},"volume":"Vol.7","number":"No.2","starting_page":"85","ending_page":"95","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/tkm2.1249"],"issn":["2053-4515"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115430","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33148907","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=373460","label":"url"}],"paper_title":{"en":"Effects of corticosteroid on mRNA levels of histamine H1 receptor in nasal mucosa of healthy participants and HeLa cells.","ja":"Effects of corticosteroid on mRNA levels of histamine H1 receptor in nasal mucosa of healthy participants and HeLa cells."},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Kamimura Seiichiro"},{"name":"Fujii Tatsuya"},{"name":"Mizuguchi Hiroyuki"},{"name":"Naito Keisuke"},{"name":"Kondou Eiji"},{"name":"Matsuda Kazunori"},{"name":"Azuma Takahiro"},{"name":"Satou Gou"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"神村 盛一郎"},{"name":"藤井 達也"},{"name":"水口 博之"},{"name":"Naito Keisuke"},{"name":"近藤 英司"},{"name":"松田 和徳"},{"name":"東 貴弘"},{"name":"佐藤 豪"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"The purpose of this study is to examine the effect of intranasal corticosteroid (INCS) administration on histamine H1 receptor (H1R) gene expression in the nasal mucosa of healthy participants and the effects of dexamethasone on basal and histamine-induced H1R mRNA expression, and histamine-induced phosphorylation of extracellular signal-regulated kinase (ERK) in HeLa cells. Sixteen healthy participants were given INCS once daily for a week. After pretreatment of dexamethasone, HeLa cells were treated with histamine. Levels of H1R mRNA and phosphorylation of ERK were measured using real time PCR and immunoblot analysis, respectively. Levels of H1R mRNA in the nasal mucosa of healthy participants receiving INCS was significantly decreased. Dexamethasone suppressed basal levels of H1R mRNA, and histamine-induced up-regulation of H1R mRNA and ERK phosphorylation in HeLa cells. These data suggested that corticosteroid inhibited both basal transcription and histamine-induced transcriptional activation of H1R through its suppression of ERK phosphorylation in the signaling pathway involved in H1R gene transcription. It is further suggested that pre-seasonal prophylactic administration of INCS suppresses both basal and pollen-induced upregulation of H1R gene expression in the nasal mucosa of patients with pollinosis, leading to prevention of the exacerbation of nasal symptoms during peak pollen season. J. Med. Invest. 67 : 311-314, August, 2020.","ja":"The purpose of this study is to examine the effect of intranasal corticosteroid (INCS) administration on histamine H1 receptor (H1R) gene expression in the nasal mucosa of healthy participants and the effects of dexamethasone on basal and histamine-induced H1R mRNA expression, and histamine-induced phosphorylation of extracellular signal-regulated kinase (ERK) in HeLa cells. Sixteen healthy participants were given INCS once daily for a week. After pretreatment of dexamethasone, HeLa cells were treated with histamine. Levels of H1R mRNA and phosphorylation of ERK were measured using real time PCR and immunoblot analysis, respectively. Levels of H1R mRNA in the nasal mucosa of healthy participants receiving INCS was significantly decreased. Dexamethasone suppressed basal levels of H1R mRNA, and histamine-induced up-regulation of H1R mRNA and ERK phosphorylation in HeLa cells. These data suggested that corticosteroid inhibited both basal transcription and histamine-induced transcriptional activation of H1R through its suppression of ERK phosphorylation in the signaling pathway involved in H1R gene transcription. It is further suggested that pre-seasonal prophylactic administration of INCS suppresses both basal and pollen-induced upregulation of H1R gene expression in the nasal mucosa of patients with pollinosis, leading to prevention of the exacerbation of nasal symptoms during peak pollen season. J. Med. Invest. 67 : 311-314, August, 2020."},"publication_date":"2020-08","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.67","number":"No.3.4","starting_page":"311","ending_page":"314","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.67.311"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115427","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33148904","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=373459","label":"url"}],"paper_title":{"en":"Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression.","ja":"Identification of pyrogallol from Awa-tea as an anti-allergic compound that suppresses nasal symptoms and IL-9 gene expression."},"authors":{"en":[{"name":"Nakano Tomohiro"},{"name":"Ikeda Mitsuhiro"},{"name":"Wakugawa Tomoharu"},{"name":"Kashiwada Yoshiki"},{"name":"Kaminuma Osamu"},{"name":"Kitamura Noriko"},{"name":"Yabumoto Masam"},{"name":"Fujino Hiromichi"},{"name":"Kitamura Yoshiaki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"},{"name":"Mizuguchi Hiroyuki"}],"ja":[{"name":"Nakano Tomohiro"},{"name":"Ikeda Mitsuhiro"},{"name":"Wakugawa Tomoharu"},{"name":"Kashiwada Yoshiki"},{"name":"Kaminuma Osamu"},{"name":"Kitamura Noriko"},{"name":"Yabumoto Masam"},{"name":"Fujino Hiromichi"},{"name":"北村 嘉章"},{"name":"福井 裕行"},{"name":"武田 憲昭"},{"name":"水口 博之"}]},"description":{"en":"As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020.","ja":"As the expression level of allergic disease sensitive genes are correlated with the severity of allergic symptoms, suppression of these gene expressions could be promising therapeutics. We demonstrated that protein kinase Cδ / heat shock protein 90-mediated H1R gene expression signaling and nuclear factor of activated T-cells (NFAT)-mediated IL-9 gene expression signaling are responsible for the pathogenesis of pollinosis. Treatment with Awa-tea combined with wild grape hot water extract suppressed these signaling and alleviated nasal symptoms in toluene-2,4-diisocyanate (TDI)-sensitized rats. However, the underlying mechanism of its anti-allergic activity is not elucidated yet. Here, we sought to identify an anti-allergic compound from Awa-tea and pyrogallol was identified as an active compound. Pyrogallol strongly suppressed ionomycin-induced up-regulation of IL-9 gene expression in RBL-2H3 cells. Treatment with pyrogallol in combination with epinastine alleviated nasal symptoms and suppressed up-regulation of IL-9 gene expression in TDI-sensitized rats. Pyrogallol itself did not inhibit calcineurin phosphatase activity. However, pyrogallol suppressed ionomycin-induced dephosphorylation and nuclear translocation of NFAT. These data suggest pyrogallol is an anti-allergic compound in Awa-tea and it suppressed NFAT-mediated IL-9 gene expression through the inhibition of dephosphorylation of NFAT. This might be the underlying mechanism of the therapeutic effects of combined therapy of pyrogallol with antihistamine. J. Med. Invest. 67 : 289-297, August, 2020."},"publication_date":"2020-08","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.67","number":"No.3.4","starting_page":"289","ending_page":"297","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.67.289"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=375893","label":"url"}],"paper_title":{"en":"ヒスタミンH1受容体とIL-33遺伝子発現亢進に対する小青竜湯の抑制効果","ja":"ヒスタミンH1受容体とIL-33遺伝子発現亢進に対する小青竜湯の抑制効果"},"authors":{"en":[{"name":"Nakano Seiichi"},{"name":"Kitamura Yoshiaki"},{"name":"Kamimura Seiichiro"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"中野 誠一"},{"name":"北村 嘉章"},{"name":"神村 盛一郎"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"publication_date":"2020-04-09","publication_name":{"en":"Japanese Journal of Rhinology","ja":"日本鼻科学会会誌"},"volume":"Vol.59","number":"No.1","starting_page":"73","ending_page":"74","languages":["jpn"],"referee":true,"identifiers":{"doi":["10.7248/jjrhi.59.73"],"issn":["1883-7077"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112928","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30301597","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=353059","label":"url"}],"paper_title":{"en":"Effects of irradiation with narrowband-ultraviolet B on up-regulation of histamine H1 receptor mRNA and induction of apoptosis in HeLa cells and nasal mucosa of rats.","ja":"Effects of irradiation with narrowband-ultraviolet B on up-regulation of histamine H1 receptor mRNA and induction of apoptosis in HeLa cells and nasal mucosa of rats."},"authors":{"en":[{"name":"Fujii Tatsuya"},{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Okamoto Kentaroh"},{"name":"Sanada Nanae"},{"name":"Yamada Takuya"},{"name":"Sugiyama Manabu"},{"name":"Michinaga Shotaro"},{"name":"Kitayama Mika"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"藤井 達也"},{"name":"北村 嘉章"},{"name":"水口 博之"},{"name":"Okamoto Kentaroh"},{"name":"Sanada Nanae"},{"name":"Yamada Takuya"},{"name":"Sugiyama Manabu"},{"name":"Michinaga Shotaro"},{"name":"Kitayama Mika"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"once a day for three days suppressed TDI-induced sneezes and up-regulation of H1R mRNA in nasal mucosa without induction of apoptosis. These findings suggest that repeated intranasal irradiation with low dose of NB-UVB could be clinically used as phototherapy of AR.","ja":", irradiation with 310 nm NB-UVB induced apoptosis. Western blot analysis showed that the suppressive effect of NB-UVB irradiation on H1R gene expression was through the inhibition of ERK phosphorylation. In TDI-sensitized rat, intranasal irradiation with 310 nm NB-UVB at an estimated dose of 100 mJ/cm"},"publication_date":"2018-09-10","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.138","number":"No.1","starting_page":"54","ending_page":"62","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2018.08.011"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30175778","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=353061","label":"url"}],"paper_title":{"en":"Receptor and Interleukin-9 Gene Expressions Responsible for the Pathogenesis of the Allergic Rhinitis.","ja":"Receptor and Interleukin-9 Gene Expressions Responsible for the Pathogenesis of the Allergic Rhinitis."},"authors":{"en":[{"name":"Shaha Aurpita"},{"name":"Mizuguchi Hiroyuki"},{"name":"Kitamura Yoshiaki"},{"name":"Fujino Hiromichi"},{"name":"Yabumoto Masami"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Shaha Aurpita"},{"name":"水口 博之"},{"name":"北村 嘉章"},{"name":"藤野 裕道"},{"name":"Yabumoto Masami"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"phosphorylation of PKCδ in HeLa cells. In RBL-2H3 cells, RJ and BGPP also suppressed NFAT-mediated IL-9 gene expression. These results suggest that RJ and BGPP improve allergic symptoms by suppressing PKCδ and NFAT signaling pathways, two important signal pathways for the AR pathogenesis, and suggest that RJ and BGPP could be good therapeutics against AR.","ja":"phosphorylation of PKCδ in HeLa cells. In RBL-2H3 cells, RJ and BGPP also suppressed NFAT-mediated IL-9 gene expression. These results suggest that RJ and BGPP improve allergic symptoms by suppressing PKCδ and NFAT signaling pathways, two important signal pathways for the AR pathogenesis, and suggest that RJ and BGPP could be good therapeutics against AR."},"publication_date":"2018","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"Vol.41","number":"No.9","starting_page":"1440","ending_page":"1447","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b18-00325"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112246","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30282868","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=353060","label":"url"}],"paper_title":{"en":"Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis.","ja":"Effect of wild grape on the signaling of histamine H1 receptor gene expression responsible for the pathogenesis of allergic rhinitis."},"authors":{"en":[{"name":"Islam Rezwanul"},{"name":"Mizuguchi Hiroyuki"},{"name":"Shaha Aurpita"},{"name":"Nishida Kohei"},{"name":"Yabumoto Masami"},{"name":"Ikeda Hisashi"},{"name":"Fujino Hiromichi"},{"name":"Kitamura Yoshiaki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"Islam Rezwanul"},{"name":"水口 博之"},{"name":"Shaha Aurpita"},{"name":"Nishida Kohei"},{"name":"Yabumoto Masami"},{"name":"Ikeda Hisashi"},{"name":"藤野 裕道"},{"name":"北村 嘉章"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018.","ja":"receptor (H1R) and IL-9 gene expressions, respectively, are responsible for the pathogenesis of allergic rhinitis. We explore anti-allergic compounds that suppress these signaling pathways and found that wild grape (WG) contains such compounds. Here, we investigated the effect of WG hot water extract (WGE) on the signaling pathways for PKCδ-mediated H1R and NFAT-mediated IL-9 gene expressions. WGE suppressed histamine/PMA-induced H1R gene up-regulation in HeLa cells. Toluene-2,4-diisocyanate (TDI)-induced H1R mRNA elevation in TDI-sensitized rats was also suppressed by WGE treatment. Treatment with WGE in combination with Awa-tea, suppresses NFAT signaling-mediated IL-9 gene, markedly alleviated nasal symptoms. Furthermore, WGE suppressed PMA-induced IL-33 gene up-regulation in Swiss 3T3 cells. Data suggest that combination of WGE, suppresses PKCδ signaling with Awa-tea, suppresses NFAT signaling would have distinct clinical and therapeutic advantages as a substitute for anti-allergic drugs. In addition, as the expression level of IL-33 mRNA was correlated with the blood eosinophils number in patients with pollinosis, WG could alleviate eosinophilic inflammation through the suppression of IL-33 gene expression. J. Med. Invest. 65:242-250, August, 2018."},"publication_date":"2018","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.65","number":"No.3.4","starting_page":"242","ending_page":"250","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.65.242"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111099","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28373608","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85016425921&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=323288","label":"url"}],"paper_title":{"en":"Protein kinase C-δ signaling regulates glucagon secretion from pancreatic islets","ja":"Protein kinase C-δ signaling regulates glucagon secretion from pancreatic islets"},"authors":{"en":[{"name":"Yamamoto Kiyotake"},{"name":"Mizuguchi Hiroyuki"},{"name":"Tokashiki Natsumi"},{"name":"Kobayashi Makoto"},{"name":"Tamaki Motoyuki"},{"name":"Sato Youichi"},{"name":"Fukui Hiroyuki"},{"name":"Yamauchi Aiko"}],"ja":[{"name":"山本 清威"},{"name":"水口 博之"},{"name":"Tokashiki Natsumi"},{"name":"Kobayashi Makoto"},{"name":"田蒔 基行"},{"name":"佐藤 陽一"},{"name":"福井 裕行"},{"name":"山内 あい子"}]},"description":{"en":"Accumulating evidence supports the \"glucagonocentric hypothesis\", in which antecedent -cell failure and inhibition of glucagon secretion are responsible for diabetes progression. Protein kinase C (PKC) is involved in glucagon secretion from -cells, although which PKC isozyme is involved and the mechanism underlying this PKC-regulated glucagon secretion remains unknown. Here, the involvement of PKC in the onset and progression of diabetes was elucidated. Immunofluorescence studies revealed that PKC was expressed and activated in -cells of STZ-induced diabetic model mice. Phorbol 12-myristate 13-acetate (PMA) stimulation significantly augmented glucagon secretion from isolated islets. Pre-treatment with quercetin and rottlerin, PKC signaling inhibitors, significantly suppressed the PMA-induced elevation of glucagon secretion. While Go6976, a Ca(2+)-dependent PKC selective inhibitor did not suppress glucagon secretion. Quercetin suppressed PMA-induced phosphorylation of Tyr(311) of PKC in isolated islets. However, quercetin itself had no effect on either glucagon secretion or glucagon mRNA expression. Our data suggest that PKC signaling inhibitors suppressed glucagon secretion. Elucidation of detailed signaling pathways causing PKC activation in the onset and progression of diabetes followed by the augmentation of glucagon secretion could lead to the identification of novel therapeutic target molecules and the development of novel therapeutic drugs for diabetes. J. Med. Invest. 64: 122-128, February, 2017.","ja":"Accumulating evidence supports the \"glucagonocentric hypothesis\", in which antecedent -cell failure and inhibition of glucagon secretion are responsible for diabetes progression. Protein kinase C (PKC) is involved in glucagon secretion from -cells, although which PKC isozyme is involved and the mechanism underlying this PKC-regulated glucagon secretion remains unknown. Here, the involvement of PKC in the onset and progression of diabetes was elucidated. Immunofluorescence studies revealed that PKC was expressed and activated in -cells of STZ-induced diabetic model mice. Phorbol 12-myristate 13-acetate (PMA) stimulation significantly augmented glucagon secretion from isolated islets. Pre-treatment with quercetin and rottlerin, PKC signaling inhibitors, significantly suppressed the PMA-induced elevation of glucagon secretion. While Go6976, a Ca(2+)-dependent PKC selective inhibitor did not suppress glucagon secretion. Quercetin suppressed PMA-induced phosphorylation of Tyr(311) of PKC in isolated islets. However, quercetin itself had no effect on either glucagon secretion or glucagon mRNA expression. Our data suggest that PKC signaling inhibitors suppressed glucagon secretion. Elucidation of detailed signaling pathways causing PKC activation in the onset and progression of diabetes followed by the augmentation of glucagon secretion could lead to the identification of novel therapeutic target molecules and the development of novel therapeutic drugs for diabetes. J. Med. Invest. 64: 122-128, February, 2017."},"publication_date":"2017-02","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.64","number":"No.1,2","starting_page":"122","ending_page":"128","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.64.122"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26824787","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=320813","label":"url"}],"paper_title":{"en":"Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells","ja":"Irradiation with narrowband-ultraviolet B suppresses phorbol ester-induced up-regulation of H1 receptor mRNA in HeLa cells"},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Okamoto Kentaro"},{"name":"Kitayama, Mika"},{"name":"Fujii Tatsuya"},{"name":"Fujioka, Akira"},{"name":"Matsushita Toshio"},{"name":"Mukai Takashi"},{"name":"Kubo Yoshiaki"},{"name":"Kubo Nobuo"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"水口 博之"},{"name":"Okamoto Kentaro"},{"name":"Kitayama, Mika"},{"name":"藤井 達也"},{"name":"Fujioka, Akira"},{"name":"Matsushita Toshio"},{"name":"向井 孝志"},{"name":"久保 宜明"},{"name":"Kubo Nobuo"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis.","ja":"Conclusion These findings suggest that low dose irradiation with 310 nm NB-UVB specifically suppressed the up-regulation of H1R gene expression without inducing apoptosis and that UVB of shorter or longer wavelength than 310 nm NB-UVB had no such effects. Objective To develop a narrowband-ultraviolet B(NB-UVB) phototherapy for allergic rhinitis, this study investigated the effects of irradiation with NB-UVB at wavelength of 310 nm on phorbol-12-myristate-13-acetate (PMA)-induced up-regulation of histamine H1 receptor (H1R) mRNA in HeLa cells. Methods The mRNA levels of H1R in HeLa cells were measured using real-time RT-PCR. Apoptosis were evaluated with DNA fragmentation assay. Results PMA induced a significant increase in H1R mRNA expression in HeLa cells. Irradiation with 305 nm UVB and 310 nm NB-UVB, but not with 315 nm UVB at doses of 200 and 300 mJ/cm(2) significantly suppressed PMA-induced up-regulation of H1R mRNA. At a dose of 200 mJ/cm(2), irradiation with 305 nm UVB, but not with 310 nm NB-UVB, induced apoptosis, although exposure of the cells to both 305 and 310 nm UVB induced apoptosis at a dose of 300 mJ/cm(2) after PMA treatment in HeLa cells. Conversely, irradiation with 315 nm UVB at doses of 200 and 300 mJ/cm(2) did not induce apoptosis."},"publication_date":"2016-04","publication_name":{"en":"Acta Oto-Laryngologica","ja":"Acta Oto-Laryngologica"},"volume":"Vol.136","number":"No.4","starting_page":"409","ending_page":"413","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3109/00016489.2015.1129555"],"issn":["1651-2251"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27023331","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311116","label":"url"}],"paper_title":{"en":"Anti-bacterial and anti-inflammatory effects of ethanol extract from Houttuynia cordata poultice.","ja":"Anti-bacterial and anti-inflammatory effects of ethanol extract from Houttuynia cordata poultice."},"authors":{"en":[{"name":"Sekita Yasuko"},{"name":"Murakami Keiji"},{"name":"Yumoto Hiromichi"},{"name":"Mizuguchi Hiroyuki"},{"name":"Amoh Takashi"},{"name":"Ogino Satoshi"},{"name":"Matsuo Takashi"},{"name":"Miyake Yoichiro"},{"name":"Fukui Hiroyuki"},{"name":"Kashiwada Yoshiki"}],"ja":[{"name":"関田 泰子"},{"name":"村上 圭史"},{"name":"湯本 浩通"},{"name":"水口 博之"},{"name":"天羽 崇"},{"name":"Ogino Satoshi"},{"name":"松尾 敬志"},{"name":"三宅 洋一郎"},{"name":"福井 裕行"},{"name":"柏田 良樹"}]},"description":{"en":"Houttuynia cordata (HC) has been commonly used as many traditional remedies in local areas of Japan. Although many pharmacological activities of HC have been reported, the mechanism underlying the effect of HC remains unknown. We conducted the interview survey in Japan to verify how HC was actually used. The interview survey revealed that HC poultice (HCP) prepared from smothering fresh leaves of HC was most frequently used for the treatment of purulent skin diseases including furuncle and carbuncle with high effectiveness. Ethanol extract of HCP (eHCP) showed anti-bacterial effects against methicillin-resistant Staphylococcus aureus (MRSA), and showed an anti-biofilm activity against MRSA. eHCP showed dose-dependent inhibition of S. aureus lipoteichoic acid (LTA)-induced interleukin-8 and CCL20 production in human keratinocyte without any cytotoxicity. These results suggest that HCP is effective for skin abscess and its underlying mechanism might be the complicated multiple activities for both bacteria and host cells.","ja":"Houttuynia cordata (HC) has been commonly used as many traditional remedies in local areas of Japan. Although many pharmacological activities of HC have been reported, the mechanism underlying the effect of HC remains unknown. We conducted the interview survey in Japan to verify how HC was actually used. The interview survey revealed that HC poultice (HCP) prepared from smothering fresh leaves of HC was most frequently used for the treatment of purulent skin diseases including furuncle and carbuncle with high effectiveness. Ethanol extract of HCP (eHCP) showed anti-bacterial effects against methicillin-resistant Staphylococcus aureus (MRSA), and showed an anti-biofilm activity against MRSA. eHCP showed dose-dependent inhibition of S. aureus lipoteichoic acid (LTA)-induced interleukin-8 and CCL20 production in human keratinocyte without any cytotoxicity. These results suggest that HCP is effective for skin abscess and its underlying mechanism might be the complicated multiple activities for both bacteria and host cells."},"publication_date":"2016-03-29","publication_name":{"en":"Bioscience, Biotechnology, and Biochemistry","ja":"Bioscience, Biotechnology, and Biochemistry"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/09168451.2016.1151339"],"issn":["1347-6947"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113027","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26980430","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84960076791&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311115","label":"url"}],"paper_title":{"en":"Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats.","ja":"Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Das AK"},{"name":"Maeyama Kazutaka"},{"name":"Dev S"},{"name":"Shahriar M"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Das AK"},{"name":"前山 一隆"},{"name":"Dev S"},{"name":"Shahriar M"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R) or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC) mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI)-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.","ja":"Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R) or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC) mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI)-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription."},"publication_date":"2016-02-11","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.130","number":"No.4","starting_page":"212","ending_page":"218","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2016.02.002"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113026","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26874672","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311114","label":"url"}],"paper_title":{"en":"Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4-diisocyanate-sensitized rats.","ja":"Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4-diisocyanate-sensitized rats."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Orimoto N"},{"name":"Kadota T"},{"name":"Kominami T"},{"name":"Das AK"},{"name":"Sawada A"},{"name":"Tamada M"},{"name":"Miyagi K"},{"name":"Adachi T"},{"name":"Matsumoto M"},{"name":"Kosaka T"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Orimoto N"},{"name":"Kadota T"},{"name":"Kominami T"},{"name":"Das AK"},{"name":"Sawada A"},{"name":"Tamada M"},{"name":"Miyagi K"},{"name":"Adachi T"},{"name":"Matsumoto M"},{"name":"Kosaka T"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine.","ja":"Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI-induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine."},"publication_date":"2016-01-06","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.130","number":"No.3","starting_page":"151","ending_page":"158","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2015.12.008"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26619301","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84948402928&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311109","label":"url"}],"paper_title":{"en":"A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C--dependent signaling pathway.","ja":"A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C--dependent signaling pathway."},"authors":{"en":[{"name":"Shill Chandra Manik"},{"name":"Mizuguchi Hiroyuki"},{"name":"Karmakar Sanmoy"},{"name":"Kadota Takuya"},{"name":"Mukherjee K. Pulok"},{"name":"Kashiwada Yoshiki"},{"name":"Kitamura Yoshiaki"},{"name":"Nemoto Hisao"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Shill Chandra Manik"},{"name":"水口 博之"},{"name":"Karmakar Sanmoy"},{"name":"Kadota Takuya"},{"name":"Mukherjee K. Pulok"},{"name":"柏田 良樹"},{"name":"北村 嘉章"},{"name":"根本 尚夫"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H1 receptor (H1R) gene is upregulated in patients with allergic rhinitis (AR), and its expression level is strongly correlated with the severity of allergic symptoms. We previously reported isolation of the putative anti-allergic compound, 4-methoxybenzofuran-5-carboxamide (MBCA) from Tephrosia purpurea and its chemical synthesis (Shill et al., Bioorg Med Chem 2015;23:6869-6874). However, the mechanism underlying its anti-allergic activity remains to be elucidated. Here, we report the mechanism of MBCA on phorbol 12-myristate-13-acetate (PMA)- or histamine-induced upregulation of H1R gene expression in HeLa cells, and in vivo effects of MBCA were also determined in toluene-2,4-diisocyanate (TDI)-sensitized rats. MBCA suppressed PMA- and histamine-induced upregulation of H1R expression at both mRNA and protein levels and inhibited PMA-induced phosphorylation of PKCδ at Tyr(311) and subsequent translocation to the Golgi. Furthermore, MBCA ameliorated allergic symptoms and suppressed the elevation of H1R and helper T cell type 2 (Th2) cytokine mRNAs in TDI-sensitized rats. Data suggest that MBCA alleviates nasal symptoms in TDI-sensitized rats through the inhibition of H1R and Th2 cytokine gene expression. The mechanism of its H1R gene suppression underlies the inhibition of PKCδ activation.","ja":"Histamine H1 receptor (H1R) gene is upregulated in patients with allergic rhinitis (AR), and its expression level is strongly correlated with the severity of allergic symptoms. We previously reported isolation of the putative anti-allergic compound, 4-methoxybenzofuran-5-carboxamide (MBCA) from Tephrosia purpurea and its chemical synthesis (Shill et al., Bioorg Med Chem 2015;23:6869-6874). However, the mechanism underlying its anti-allergic activity remains to be elucidated. Here, we report the mechanism of MBCA on phorbol 12-myristate-13-acetate (PMA)- or histamine-induced upregulation of H1R gene expression in HeLa cells, and in vivo effects of MBCA were also determined in toluene-2,4-diisocyanate (TDI)-sensitized rats. MBCA suppressed PMA- and histamine-induced upregulation of H1R expression at both mRNA and protein levels and inhibited PMA-induced phosphorylation of PKCδ at Tyr(311) and subsequent translocation to the Golgi. Furthermore, MBCA ameliorated allergic symptoms and suppressed the elevation of H1R and helper T cell type 2 (Th2) cytokine mRNAs in TDI-sensitized rats. Data suggest that MBCA alleviates nasal symptoms in TDI-sensitized rats through the inhibition of H1R and Th2 cytokine gene expression. The mechanism of its H1R gene suppression underlies the inhibition of PKCδ activation."},"publication_date":"2016-01","publication_name":{"en":"International Immunopharmacology","ja":"International Immunopharmacology"},"volume":"Vol.30","starting_page":"18","ending_page":"26","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.intimp.2015.11.021"],"issn":["1878-1705"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/109692","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26598006","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311106","label":"url"}],"paper_title":{"en":"Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.","ja":"Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit."},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Nakagawa H"},{"name":"Fujii Tatsuya"},{"name":"Sakoda T"},{"name":"Enomoto T"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"Nakagawa H"},{"name":"藤井 達也"},{"name":"Sakoda T"},{"name":"Enomoto T"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders.","ja":"In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders."},"publication_date":"2015-10-30","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.129","number":"No.3","starting_page":"183","ending_page":"187","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2015.10.007"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26476665","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311102","label":"url"}],"paper_title":{"en":"The isolation and synthesis of a novel benzofuran compound from Tephrosia purpurea, and the synthesis of several related derivatives, which suppress histamine H1 receptor gene expression.","ja":"The isolation and synthesis of a novel benzofuran compound from Tephrosia purpurea, and the synthesis of several related derivatives, which suppress histamine H1 receptor gene expression."},"authors":{"en":[{"name":"Shill M C"},{"name":"Das AK"},{"name":"Itou T"},{"name":"Karmakar S"},{"name":"Mukherjee PK"},{"name":"Mizuguchi Hiroyuki"},{"name":"Kashiwada Yoshiki"},{"name":"Fukui Hiroyuki"},{"name":"Nemoto Hisao"}],"ja":[{"name":"Shill M C"},{"name":"Das AK"},{"name":"Itou T"},{"name":"Karmakar S"},{"name":"Mukherjee PK"},{"name":"水口 博之"},{"name":"柏田 良樹"},{"name":"福井 裕行"},{"name":"根本 尚夫"}]},"description":{"en":"A novel naturally occurring compound with a benzofuran skeleton was isolated from a plant, Tephrosia purpurea collected in Bangladesh. The chemical synthesis of this compound confirmed its structure, and preliminary biological results showed its suppressive activity towards histamine H1 gene expression. One isomer and four derivatives were also synthesized, and their suppression activity was investigated. Although only small quantities of this compound can be isolated from its natural source, a 10 g scale synthesis was demonstrated by the newly developed method.","ja":"A novel naturally occurring compound with a benzofuran skeleton was isolated from a plant, Tephrosia purpurea collected in Bangladesh. The chemical synthesis of this compound confirmed its structure, and preliminary biological results showed its suppressive activity towards histamine H1 gene expression. One isomer and four derivatives were also synthesized, and their suppression activity was investigated. Although only small quantities of this compound can be isolated from its natural source, a 10 g scale synthesis was demonstrated by the newly developed method."},"publication_date":"2015-10-21","publication_name":{"en":"Bioorganic & Medicinal Chemistry","ja":"Bioorganic & Medicinal Chemistry"},"volume":"Vol.23","number":"No.21","starting_page":"6869","ending_page":"6874","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bmc.2015.09.049"],"issn":["1464-3391"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26391399","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311105","label":"url"}],"paper_title":{"en":"Disruption of Heat Shock Protein 90 (Hsp90)-Protein Kinase Cδ (PKCδ) Interaction by (-)-Maackiain Suppresses Histamine H1 Receptor Gene Transcription in HeLa Cells","ja":"Disruption of Heat Shock Protein 90 (Hsp90)-Protein Kinase Cδ (PKCδ) Interaction by (-)-Maackiain Suppresses Histamine H1 Receptor Gene Transcription in HeLa Cells"},"authors":{"en":[{"name":"Nariai Yuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Ogasawara T"},{"name":"Nagai H"},{"name":"Sasaki Y"},{"name":"Okamoto Y"},{"name":"Yoshimura Yoshiyuki"},{"name":"Kitamura Yoshiaki"},{"name":"Nemoto Hisao"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"成相 祐希"},{"name":"水口 博之"},{"name":"Ogasawara T"},{"name":"Nagai H"},{"name":"Sasaki Y"},{"name":"Okamoto Y"},{"name":"吉村 好之"},{"name":"北村 嘉章"},{"name":"根本 尚夫"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"The histamine H1 receptor (H1R) gene is an allergic disease sensitive gene, and its expression level is strongly correlated with the severity of allergic symptoms. (-)-Maackiain was identified as a Kujin-derived anti-allergic compound that suppresses the up-regulation of the H1R gene. However, the underlying mechanism of H1R gene suppression remains unknown. Here, we sought to identify a target protein of (-)-maackiain and investigate its mechanism of action. A fluorescence quenching assay and immunoblot analysis identified heat shock protein 90 (Hsp90) as a target protein of (-)-maackiain. A pull-down assay revealed that (-)-maackiain disrupted the interaction of Hsp90 with PKCδ, resulting in the suppression of phorbol 12-myristate 13-acetate (PMA)-induced up-regulation of H1R gene expression in HeLa cells. Additional Hsp90 inhibitors, including 17-(allylamino)-17-demethoxygeldanamycin, celastrol, and novobiocin also suppressed PMA-induced H1R gene up-regulation. 17-(Allylamino)-17-demethoxygeldanamycin inhibited PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ. These data suggest that (-)-maackiain is a novel Hsp90 pathway inhibitor. The underlying mechanism of the suppression of PMA-induced up-regulation of H1R gene expression by (-)-maackiain and Hsp90 inhibitors is the inhibition of PKCδ activation through the disruption of Hsp90-PKCδ interaction. Involvement of Hsp90 in H1R gene up-regulation suggests that suppression of the Hsp90 pathway could be a novel therapeutic strategy for allergic rhinitis.","ja":"The histamine H1 receptor (H1R) gene is an allergic disease sensitive gene, and its expression level is strongly correlated with the severity of allergic symptoms. (-)-Maackiain was identified as a Kujin-derived anti-allergic compound that suppresses the up-regulation of the H1R gene. However, the underlying mechanism of H1R gene suppression remains unknown. Here, we sought to identify a target protein of (-)-maackiain and investigate its mechanism of action. A fluorescence quenching assay and immunoblot analysis identified heat shock protein 90 (Hsp90) as a target protein of (-)-maackiain. A pull-down assay revealed that (-)-maackiain disrupted the interaction of Hsp90 with PKCδ, resulting in the suppression of phorbol 12-myristate 13-acetate (PMA)-induced up-regulation of H1R gene expression in HeLa cells. Additional Hsp90 inhibitors, including 17-(allylamino)-17-demethoxygeldanamycin, celastrol, and novobiocin also suppressed PMA-induced H1R gene up-regulation. 17-(Allylamino)-17-demethoxygeldanamycin inhibited PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ. These data suggest that (-)-maackiain is a novel Hsp90 pathway inhibitor. The underlying mechanism of the suppression of PMA-induced up-regulation of H1R gene expression by (-)-maackiain and Hsp90 inhibitors is the inhibition of PKCδ activation through the disruption of Hsp90-PKCδ interaction. Involvement of Hsp90 in H1R gene up-regulation suggests that suppression of the Hsp90 pathway could be a novel therapeutic strategy for allergic rhinitis."},"publication_date":"2015-09-21","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.290","number":"No.45","starting_page":"27393","ending_page":"27402","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M115.657023"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/115685","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26516579","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=311101","label":"url"}],"paper_title":{"en":"Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes.","ja":"Maackiain is a novel antiallergic compound that suppresses transcriptional upregulation of the histamine H1 receptor and interleukin-4 genes."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Nariai Y"},{"name":"Kato S"},{"name":"Nakano T"},{"name":"Kanayama T"},{"name":"Kashiwada Yoshiki"},{"name":"Nemoto Hisao"},{"name":"Kawazoe Kazuyoshi"},{"name":"Takaishi Yoshihisa"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Nariai Y"},{"name":"Kato S"},{"name":"Nakano T"},{"name":"Kanayama T"},{"name":"柏田 良樹"},{"name":"根本 尚夫"},{"name":"川添 和義"},{"name":"高石 喜久"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (-)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (-)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ, which led to the suppression of H1R gene transcription. However, (-)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (-)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation.","ja":"Kujin contains antiallergic compounds that inhibit upregulation of histamine H1 receptor (H1R) and interleukin (IL)-4 gene expression. However, the underlying mechanism remains unknown. We sought to identify a Kujin-derived antiallergic compound and investigate its mechanism of action. The H1R and IL-4 mRNA levels were determined by real-time quantitative RT-PCR. To investigate the effects of maackiain in vivo, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as a nasal hypersensitivity animal model. We identified (-)-maackiain as the responsible component. Synthetic maackiain showed stereoselectivity for the suppression of IL-4 gene expression but not for H1R gene expression, suggesting distinct target proteins for transcriptional signaling. (-)-Maackiain inhibited of PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ, which led to the suppression of H1R gene transcription. However, (-)-maackiain did not show any antioxidant activity or inhibition of PKCδ enzymatic activity per se. Pretreatment with maackiain alleviated nasal symptoms and suppressed TDI-induced upregulations of H1R and IL-4 gene expressions in TDI-sensitized rats. These data suggest that (-)-maackiain is a novel antiallergic compound that alleviates nasal symptoms in TDI-sensitized allergy model rats through the inhibition of H1R and IL-4 gene expression. The molecular mechanism underlying its suppressive effect for H1R gene expression is mediated by the inhibition of PKCδ activation."},"publication_date":"2015-08-10","publication_name":{"en":"Pharmacology Research & Perspectives","ja":"Pharmacology Research & Perspectives"},"volume":"Vol.3","number":"No.5","starting_page":"e00166","ending_page":"e00166","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/prp2.166"],"issn":["2052-1707"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/130003395637/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204272547840/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84897512112&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=296629","label":"url"}],"paper_title":{"en":"The Molecular Mechanism of Up-regulation of Histamine H1 Receptor mRNA in the Nasal Mucosa of Patients with Allergic Rhinitis and the Effect of Antihistamine on Histamine H1 Receptor Expression","ja":"アレルギー性鼻炎におけるヒスタミンH1受容体遺伝子発現亢進の分子機構とその制御"},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"We are focusing on the histamine H1 receptor (H1R) as an allergic disease-sensitive gene. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression levels. We discovered that the direct stimulation of H1R induced the up-regulation of H1R gene expression through PKCδ activation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Antihistamines have three effects: the blocking effect on histamine signaling of H1 receptors; the suppressive effect on histamine-induced up-regulation of H1R mRNA that is the transcriptional activation of H1R; and the suppressive effect on H1R mRNA in the absence of histamine that is the basal transcription of H1R. The third effect may be another side of the inverse agonist action of antihistamine. We demonstrated that repeated pretreatment with antihistamines in the allergic rhinitis model rats resulted not only in the improvement of symptoms but also in the suppression of the up-regulation of H1R mRNA in the nasal mucosa. We next investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of H1R mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. These results suggest that H1R is an allergic disease-sensitive gene and H1R plays an important role in allergic rhinitis through the regulation of histamine signaling.","ja":"We are focusing on the histamine H1 receptor (H1R) as an allergic disease-sensitive gene. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression levels. We discovered that the direct stimulation of H1R induced the up-regulation of H1R gene expression through PKCδ activation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Antihistamines have three effects: the blocking effect on histamine signaling of H1 receptors; the suppressive effect on histamine-induced up-regulation of H1R mRNA that is the transcriptional activation of H1R; and the suppressive effect on H1R mRNA in the absence of histamine that is the basal transcription of H1R. The third effect may be another side of the inverse agonist action of antihistamine. We demonstrated that repeated pretreatment with antihistamines in the allergic rhinitis model rats resulted not only in the improvement of symptoms but also in the suppression of the up-regulation of H1R mRNA in the nasal mucosa. We next investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of H1R mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. These results suggest that H1R is an allergic disease-sensitive gene and H1R plays an important role in allergic rhinitis through the regulation of histamine signaling."},"publication_date":"2014-04","publication_name":{"en":"Practica Oto-Rhino-Laryngologica","ja":"耳鼻咽喉科臨床"},"volume":"Vol.107","number":"No.4","starting_page":"261","ending_page":"270","languages":["jpn"],"referee":true,"identifiers":{"doi":["10.5631/jibirin.107.261"],"issn":["0032-6313"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23615224","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84878131133&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=276111","label":"url"}],"paper_title":{"en":"Combination of leukotoriene receptor antagonist with antihistamine has an additive suppressive effect on the up-regulation of H1-receptor mRNA in the nasal mucosa of toluene 2,4-diisocyanate-sensitized rat.","ja":"Combination of leukotoriene receptor antagonist with antihistamine has an additive suppressive effect on the up-regulation of H1-receptor mRNA in the nasal mucosa of toluene 2,4-diisocyanate-sensitized rat."},"authors":{"en":[{"name":"Kuroda Wakana"},{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Miyamoto Yuko"},{"name":"Kalubi Bukasa"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"Kuroda Wakana"},{"name":"北村 嘉章"},{"name":"水口 博之"},{"name":"Miyamoto Yuko"},{"name":"カルビ ブカサ"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation.","ja":"An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation."},"publication_date":"2013-04-25","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.122","number":"No.1","starting_page":"55","ending_page":"58","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.12250SC"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23333628","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=276106","label":"url"}],"paper_title":{"en":"Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells.","ja":"Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells."},"authors":{"en":[{"name":"Hattori Masashi"},{"name":"Mizuguchi Hiroyuki"},{"name":"Baba Yuko"},{"name":"Ono Shohei"},{"name":"Nakano Tomohiro"},{"name":"Zhang Qian"},{"name":"Sasaki Yohei"},{"name":"Kobayashi Makoto"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Hattori Masashi"},{"name":"水口 博之"},{"name":"Baba Yuko"},{"name":"Ono Shohei"},{"name":"Nakano Tomohiro"},{"name":"Zhang Qian"},{"name":"Sasaki Yohei"},{"name":"Kobayashi Makoto"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"It has been reported that the histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis and H1R expression level strongly correlates with the severity of allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful anti-allergic medications. Recently, we demonstrated that histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the protein kinase C (PKC)/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously. Quercetin is one of the well-characterized flavonoids and it possesses many biological activities including anti-allergic activity. However, effect of quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of quercetin on histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized allergy model rats. Quercetin suppressed histamine- and PMA-induced up-regulation of H1R gene expression. Quercetin also inhibited histamine- or PMA-induced phosphorylation of Tyr(311) of PKC and translocation of PKC to the Golgi. Pre-treatment with quercetin for 3weeks suppressed TDI-induced nasal allergy-like symptoms and elevation of H1R mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that quercetin suppresses H1R gene expression by the suppression of PKC activation through the inhibition of its translocation to the Golgi.","ja":"It has been reported that the histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis and H1R expression level strongly correlates with the severity of allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful anti-allergic medications. Recently, we demonstrated that histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the protein kinase C (PKC)/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously. Quercetin is one of the well-characterized flavonoids and it possesses many biological activities including anti-allergic activity. However, effect of quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of quercetin on histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized allergy model rats. Quercetin suppressed histamine- and PMA-induced up-regulation of H1R gene expression. Quercetin also inhibited histamine- or PMA-induced phosphorylation of Tyr(311) of PKC and translocation of PKC to the Golgi. Pre-treatment with quercetin for 3weeks suppressed TDI-induced nasal allergy-like symptoms and elevation of H1R mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that quercetin suppresses H1R gene expression by the suppression of PKC activation through the inhibition of its translocation to the Golgi."},"publication_date":"2013-01-16","publication_name":{"en":"International Immunopharmacology","ja":"International Immunopharmacology"},"volume":"Vol.15","number":"No.2","starting_page":"232","ending_page":"239","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.intimp.2012.12.030"],"issn":["1878-1705"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23209876","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=263255","label":"url"}],"paper_title":{"en":"PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor.","ja":"PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H1 receptor."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Kohei Miyagi"},{"name":"Takuma Terao,"},{"name":"Noriko Sakamoto"},{"name":"Yosuke Yamawaki"},{"name":"Tsubasa Adachi,"},{"name":"S. Ono,"},{"name":"Y. Sasaki,"},{"name":"Yoshimura Yoshiyuki"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Kohei Miyagi"},{"name":"Takuma Terao,"},{"name":"Noriko Sakamoto"},{"name":"Yosuke Yamawaki"},{"name":"Tsubasa Adachi,"},{"name":"S. Ono,"},{"name":"Y. Sasaki,"},{"name":"吉村 好之"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"publication_date":"2012-12","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"Vol.2","starting_page":"916","ending_page":"916","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/srep00916"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22677810","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=251751","label":"url"}],"paper_title":{"en":"Identification of a histaminergic circuit in the caudal hypothalamus: An evidence for functional heterogeneity of histaminergic neurons.","ja":"Identification of a histaminergic circuit in the caudal hypothalamus: An evidence for functional heterogeneity of histaminergic neurons."},"authors":{"en":[{"name":"Umehara Hayato"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"梅原 隼人"},{"name":"水口 博之"},{"name":"福井 裕行"}]},"description":{"en":"It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic neurons have not been fully mapped so far. To address this issue, we have investigated antihistamine-sensitive neuronal activation in the hypothalamus to determine the hypothalamic region primarily innervated by histaminergic neurons. Here we review our recent findings showing the existence of the heterogeneous subpopulations of histaminergic neurons in the TMN that innervated distinct regions to regulate particular functions. We have identified the caudal part of the arcuate nucleus of hypothalamus (cARC) as a target region of histaminergic neurons in food-restricted rats by assessing suppression of c-Fos expression by pretreatment with antihistamines. Histaminergic neurons in the tuberomammillary nucleus (TMN) are morphologically subdivided into five groups (E1-E5). Among the subdivisions, the E3 group was found to be activated corresponding to the activation of cARC neurons. Our findings suggest that this subpopulation selectively innervate cARC neurons. Accumulating reports have also described c-Fos expression in other TMN subpopulations. Various stress challenge induced c-Fos expression primarily in E4 and E5 subpopulations. Motivation- and drug-induced arousal elicited in common activation of ventrolateral part of the TMN containing E1 and E2 subdivisions, which receive projections from wake-active orexin neurons and sleep-active GABA neurons. These lines of evidence support the hypothesis that there are heterogeneous subpopulations in the TMN that innervated distinct regions to regulate particular functions.","ja":"It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic neurons have not been fully mapped so far. To address this issue, we have investigated antihistamine-sensitive neuronal activation in the hypothalamus to determine the hypothalamic region primarily innervated by histaminergic neurons. Here we review our recent findings showing the existence of the heterogeneous subpopulations of histaminergic neurons in the TMN that innervated distinct regions to regulate particular functions. We have identified the caudal part of the arcuate nucleus of hypothalamus (cARC) as a target region of histaminergic neurons in food-restricted rats by assessing suppression of c-Fos expression by pretreatment with antihistamines. Histaminergic neurons in the tuberomammillary nucleus (TMN) are morphologically subdivided into five groups (E1-E5). Among the subdivisions, the E3 group was found to be activated corresponding to the activation of cARC neurons. Our findings suggest that this subpopulation selectively innervate cARC neurons. Accumulating reports have also described c-Fos expression in other TMN subpopulations. Various stress challenge induced c-Fos expression primarily in E4 and E5 subpopulations. Motivation- and drug-induced arousal elicited in common activation of ventrolateral part of the TMN containing E1 and E2 subdivisions, which receive projections from wake-active orexin neurons and sleep-active GABA neurons. These lines of evidence support the hypothesis that there are heterogeneous subpopulations in the TMN that innervated distinct regions to regulate particular functions."},"publication_date":"2012-06-05","publication_name":{"en":"Neurochemistry International","ja":"Neurochemistry International"},"volume":"Vol.61","number":"No.6","starting_page":"942","ending_page":"947","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.neuint.2012.05.022"],"issn":["1872-9754"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22216765","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=251748","label":"url"}],"paper_title":{"en":"Preseasonal prophylactic treatment with antihistamines suppresses IL-5 but not IL-33 mRNA expression in the nasal mucosa of patients with seasonal allergic rhinitis caused by Japanese cedar pollen.","ja":"Preseasonal prophylactic treatment with antihistamines suppresses IL-5 but not IL-33 mRNA expression in the nasal mucosa of patients with seasonal allergic rhinitis caused by Japanese cedar pollen."},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Ogishi Hirotaka"},{"name":"Kuroda Wakana"},{"name":"Hattori Masashi"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"水口 博之"},{"name":"Ogishi Hirotaka"},{"name":"Kuroda Wakana"},{"name":"Hattori Masashi"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen. The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated. Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period. During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA.","ja":"These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen. The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated. Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period. During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA."},"publication_date":"2012-04","publication_name":{"en":"Acta Oto-Laryngologica","ja":"Acta Oto-Laryngologica"},"volume":"Vol.132","number":"No.4","starting_page":"434","ending_page":"438","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3109/00016489.2011.644804"],"issn":["1651-2251"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22301446","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=251752","label":"url"}],"paper_title":{"en":"A report on anti-oedemogenic activity of Byttneria herbacea roots--possible involvement of histamine receptor (type I).","ja":"A report on anti-oedemogenic activity of Byttneria herbacea roots--possible involvement of histamine receptor (type I)."},"authors":{"en":[{"name":"Sarkar Lipi"},{"name":"Bhuvaneswari N"},{"name":"Samanta K. Samir"},{"name":"Islam Nurul Md"},{"name":"Sen Tuhinadri"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Karmakar Sanmoy"}],"ja":[{"name":"Sarkar Lipi"},{"name":"Bhuvaneswari N"},{"name":"Samanta K. Samir"},{"name":"Islam Nurul Md"},{"name":"Sen Tuhinadri"},{"name":"福井 裕行"},{"name":"水口 博之"},{"name":"Karmakar Sanmoy"}]},"description":{"en":"The traditional healers of the Kol tribes of West Bengal, Bihar and Jharkhand (India), widely use the woody rootstock of Byttneria herbacea to reduce the swelling of limbs, due to filariasis. Besides filariasis different part of this plant is used for the treatment of cholera, diarrhoea and asthma. This study is a preliminary attempt to evaluate the anti-oedemogenic activity of the roots of Byttneria herbacea. The anti-oedemogenic activity of the hydroalcoholic extract of the roots of Byttneria herbacea (HBH) was evaluated against carrageenan and histamine induced rat paw oedema, acetic acid induced writhing and histamine induced vascular permeability in mice. Further, the effect of HBH on the expression of human histamine receptor type I (H1R) was studied in HeLa cells. HBH exhibited significant dose-dependent inhibition (*p<0.05) against carrageenan and histamine induced rat paw oedema. Similar significant dose-dependent inhibition was observed against acetic acid induced writhing and histamine-induced vascular permeability in mice. Moreover, H1R specific mRNA expression was also significantly (*p<0.05) suppressed by HBH. HBH was observed to possess anti-oedemogenic activity which is probably mediated through suppression of H1R.","ja":"The traditional healers of the Kol tribes of West Bengal, Bihar and Jharkhand (India), widely use the woody rootstock of Byttneria herbacea to reduce the swelling of limbs, due to filariasis. Besides filariasis different part of this plant is used for the treatment of cholera, diarrhoea and asthma. This study is a preliminary attempt to evaluate the anti-oedemogenic activity of the roots of Byttneria herbacea. The anti-oedemogenic activity of the hydroalcoholic extract of the roots of Byttneria herbacea (HBH) was evaluated against carrageenan and histamine induced rat paw oedema, acetic acid induced writhing and histamine induced vascular permeability in mice. Further, the effect of HBH on the expression of human histamine receptor type I (H1R) was studied in HeLa cells. HBH exhibited significant dose-dependent inhibition (*p<0.05) against carrageenan and histamine induced rat paw oedema. Similar significant dose-dependent inhibition was observed against acetic acid induced writhing and histamine-induced vascular permeability in mice. Moreover, H1R specific mRNA expression was also significantly (*p<0.05) suppressed by HBH. HBH was observed to possess anti-oedemogenic activity which is probably mediated through suppression of H1R."},"publication_date":"2012-01-18","publication_name":{"en":"Journal of Ethnopharmacology","ja":"Journal of Ethnopharmacology"},"volume":"Vol.140","number":"No.2","starting_page":"443","ending_page":"446","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jep.2012.01.013"],"issn":["1872-7573"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22186623","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271354","label":"url"}],"paper_title":{"en":"Inverse agonistic activity of antihistamines and suppression of histamine H1 receptor gene expression.","ja":"Inverse agonistic activity of antihistamines and suppression of histamine H1 receptor gene expression."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Shohei Ono"},{"name":"Masashi Hattori"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"小野 将平"},{"name":"服部 将史"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H(1) receptor (H1R) expression influences the severity of allergy symptoms. We examined the effect of inverse agonists on H1R gene expression. Two inverse agonists (carebastine and mepyramine), but not the neutral antagonist oxatomide, decreased inositol phosphate accumulation. The inverse agonists also decreased H1R gene expression and down-regulated H1R mRNA below basal expression, while basal H1R mRNA expression was maintained after oxatomide treatment. These results suggest that inverse agonists more potently alleviate allergy symptoms by not only inhibiting stimulus-induced up-regulation of H1R gene expression but also by suppressing basal histamine signaling through their inverse agonistic activity.","ja":"Histamine H(1) receptor (H1R) expression influences the severity of allergy symptoms. We examined the effect of inverse agonists on H1R gene expression. Two inverse agonists (carebastine and mepyramine), but not the neutral antagonist oxatomide, decreased inositol phosphate accumulation. The inverse agonists also decreased H1R gene expression and down-regulated H1R mRNA below basal expression, while basal H1R mRNA expression was maintained after oxatomide treatment. These results suggest that inverse agonists more potently alleviate allergy symptoms by not only inhibiting stimulus-induced up-regulation of H1R gene expression but also by suppressing basal histamine signaling through their inverse agonistic activity."},"publication_date":"2012-01","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.118","number":"No.1","starting_page":"117","ending_page":"121","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.11177SC"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21782040","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=244240","label":"url"}],"paper_title":{"en":"Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions.","ja":"Albizia lebbeck suppresses histamine signaling by the inhibition of histamine H1 receptor and histidine decarboxylase gene transcriptions."},"authors":{"en":[{"name":"Nurul Islam Mohammed"},{"name":"Mizuguchi Hiroyuki"},{"name":"Shahriar Masum"},{"name":"Venkatesh Pichairajan"},{"name":"Maeyama Kazutaka"},{"name":"Mukherjee Pulok K"},{"name":"Hattori Masashi"},{"name":"Choudhuri Mohamed Sahabuddin Kabir"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Nurul Islam Mohammed"},{"name":"水口 博之"},{"name":"Shahriar Masum"},{"name":"Venkatesh Pichairajan"},{"name":"Maeyama Kazutaka"},{"name":"Mukherjee Pulok K"},{"name":"Hattori Masashi"},{"name":"Choudhuri Mohamed Sahabuddin Kabir"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network.","ja":"Histamine plays major roles in allergic diseases and its action is mediated mainly by histamine H(1) receptor (H1R). We have demonstrated that histamine signaling-related H1R and histidine decarboxylase (HDC) genes are allergic diseases sensitive genes and their expression level affects severity of the allergic symptoms. Therefore, compounds that suppress histamine signaling should be promising candidates as anti-allergic drugs. Here, we investigated the effect of the extract from the bark of Albizia lebbeck (AL), one of the ingredients of Ayruvedic medicines, on H1R and HDC gene expression using toluene-2,4-diisocyanate (TDI) sensitized allergy model rats and HeLa cells expressing endogenous H1R. Administration of the AL extract significantly decreased the numbers of sneezing and nasal rubbing. Pretreatment with the AL extract suppressed TDI-induced H1R and HDC mRNA elevations as well as [(3)H]mepyramine binding, HDC activity, and histamine content in the nasal mucosa. AL extract also suppressed TDI-induced up-regulation of IL-4, IL-5, and IL-13 mRNA. In HeLa cells, AL extract suppressed phorbol-12-myristate-13-acetate- or histamine-induced up-regulation of H1R mRNA. Our data suggest that AL alleviated nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through suppression of H1R and HDC gene transcriptions. Suppression of Th2-cytokine signaling by AL also suggests that it could affect the histamine-cytokine network."},"publication_date":"2011-07-21","publication_name":{"en":"International Immunopharmacology","ja":"International Immunopharmacology"},"volume":"Vol.11","number":"No.11","starting_page":"1766","ending_page":"1772","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.intimp.2011.07.003"],"issn":["1878-1705"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21730054","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=251741","label":"url"}],"paper_title":{"en":"Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells.","ja":"Involvement of protein kinase Cdelta/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 (PARP-1) signaling pathway in histamine-induced up-regulation of histamine H1 receptor gene expression in HeLa cells."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Terao Takuma"},{"name":"Kitai Mika"},{"name":"Ikeda Mitsuhiro"},{"name":"Yoshimura Yoshiyuki"},{"name":"Das Kumar Asish"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Terao Takuma"},{"name":"Kitai Mika"},{"name":"Ikeda Mitsuhiro"},{"name":"吉村 好之"},{"name":"Das Kumar Asish"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKC-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKC phosphorylation at Tyr(311) and Thr(505). Activation of PKC by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of PKC enhanced up-regulation of H1R gene expression, and knockdown of the PKC gene suppressed this up-regulation. Histamine or PMA caused translocation PKC from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKC/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells.","ja":"The histamine H(1) receptor (H1R) gene is up-regulated in patients with allergic rhinitis. However, the mechanism and reason underlying this up-regulation are still unknown. Recently, we reported that the H1R expression level is strongly correlated with the severity of allergic symptoms. Therefore, understanding the mechanism of this up-regulation will help to develop new anti-allergic drugs targeted for H1R gene expression. Here we studied the molecular mechanism of H1R up-regulation in HeLa cells that express H1R endogenously in response to histamine and phorbol 12-myristate 13-acetate (PMA). In HeLa cells, histamine stimulation caused up-regulation of H1R gene expression. Rottlerin, a PKC-selective inhibitor, inhibited up-regulation of H1R gene expression, but Go6976, an inhibitor of Ca(2+)-dependent PKCs, did not. Histamine or PMA stimulation resulted in PKC phosphorylation at Tyr(311) and Thr(505). Activation of PKC by H(2)O(2) resulted in H1R mRNA up-regulation. Overexpression of PKC enhanced up-regulation of H1R gene expression, and knockdown of the PKC gene suppressed this up-regulation. Histamine or PMA caused translocation PKC from the cytosol to the Golgi. U0126, an MEK inhibitor, and DPQ, a poly(ADP-ribose) polymerase-1 inhibitor, suppressed PMA-induced up-regulation of H1R gene expression. These results were confirmed by a luciferase assay using the H1R promoter. Phosphorylation of ERK and Raf-1 in response to PMA was also observed. However, real-time PCR analysis showed no inhibition of H1R mRNA up-regulation by a Raf-1 inhibitor. These results suggest the involvement of the PKC/ERK/poly(ADP-ribose) polymerase-1 signaling pathway in histamine- or PMA-induced up-regulation of H1R gene expression in HeLa cells."},"publication_date":"2011-07-05","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.286","number":"No.35","starting_page":"30542","ending_page":"30551","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M111.253104"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21601015","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=251753","label":"url"}],"paper_title":{"en":"Transcriptional microarray analysis reveals suppression of histamine signaling by Kujin alleviates allergic symptoms through down-regulation of FAT10 expression.","ja":"Transcriptional microarray analysis reveals suppression of histamine signaling by Kujin alleviates allergic symptoms through down-regulation of FAT10 expression."},"authors":{"en":[{"name":"Dev Shrabanti"},{"name":"Mizuguchi Hiroyuki"},{"name":"Das Kumar Asish"},{"name":"Baba Yoshinobu"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Dev Shrabanti"},{"name":"水口 博之"},{"name":"Das Kumar Asish"},{"name":"Baba Yoshinobu"},{"name":"福井 裕行"}]},"description":{"en":"Previously, we have shown that hot water extract from Kujin, the dried roots of Sophora flavescens alleviates allergic symptoms by suppressing histamine signaling at the transcription level in toluene 2,4-diisocyanate (TDI)-sensitized rats. To know more insights into the mechanism of the anti-allergic action of Kujin, we carried out the microarray analysis to explore genes that were up-regulated by treatment with TDI and also were suppressed these up-regulated gene expression by Kujin. Microarray analysis revealed the substantial up-regulation of FAT10 (also called UbD) mRNA due to TDI sensitization and Kujin extract significantly suppressed this up-regulation. FAT10 is an ubiquitin like protein having an active role in the immune system and is induced by proinflammatory cytokines. Activation of NF-B by FAT10 also has been reported. However, the role of FAT10 in allergic pathogenesis remains unknown. Here we investigated the correlation of FAT10-NF-B signaling with histamine signaling in TDI-sensitized rats. Real time RT-PCR analysis confirmed that treatment with TDI up-regulated FAT10 mRNA expression in the nasal mucosa of TDI-sensitized rats and Kujin extract suppressed this elevation. Treatment with H(1)-antihistamines suppressed the TDI-induced up-regulation of FAT10 mRNA expression in TDI-sensitized rats. Direct administration of histamine into the nasal cavity of non-TDI-treated normal rats up-regulated the expression of FAT10 mRNA. Our data suggest that Kujin might alleviate allergic symptoms by inhibition of NF-B activation through suppression of histamine-induced up-regulation of FAT10 mRNA expression.","ja":"Previously, we have shown that hot water extract from Kujin, the dried roots of Sophora flavescens alleviates allergic symptoms by suppressing histamine signaling at the transcription level in toluene 2,4-diisocyanate (TDI)-sensitized rats. To know more insights into the mechanism of the anti-allergic action of Kujin, we carried out the microarray analysis to explore genes that were up-regulated by treatment with TDI and also were suppressed these up-regulated gene expression by Kujin. Microarray analysis revealed the substantial up-regulation of FAT10 (also called UbD) mRNA due to TDI sensitization and Kujin extract significantly suppressed this up-regulation. FAT10 is an ubiquitin like protein having an active role in the immune system and is induced by proinflammatory cytokines. Activation of NF-B by FAT10 also has been reported. However, the role of FAT10 in allergic pathogenesis remains unknown. Here we investigated the correlation of FAT10-NF-B signaling with histamine signaling in TDI-sensitized rats. Real time RT-PCR analysis confirmed that treatment with TDI up-regulated FAT10 mRNA expression in the nasal mucosa of TDI-sensitized rats and Kujin extract suppressed this elevation. Treatment with H(1)-antihistamines suppressed the TDI-induced up-regulation of FAT10 mRNA expression in TDI-sensitized rats. Direct administration of histamine into the nasal cavity of non-TDI-treated normal rats up-regulated the expression of FAT10 mRNA. Our data suggest that Kujin might alleviate allergic symptoms by inhibition of NF-B activation through suppression of histamine-induced up-regulation of FAT10 mRNA expression."},"publication_date":"2011-05-19","publication_name":{"en":"International Immunopharmacology","ja":"International Immunopharmacology"},"volume":"Vol.11","number":"No.10","starting_page":"1504","ending_page":"1509","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.intimp.2011.05.004"],"issn":["1878-1705"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/130000451446/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282681106079744/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=235098","label":"url"}],"paper_title":{"en":"ヒスタミンH1受容体遺伝子発現機構のアレルギー疾患における病理学的意義","ja":"ヒスタミンH1受容体遺伝子発現機構のアレルギー疾患における病理学的意義"},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Kitamura Yoshiaki"},{"name":"Kondo Yuto"},{"name":"Kuroda Wakana"},{"name":"Yoshida Haruka"},{"name":"Miyamoto Yuko"},{"name":"Hattori Masashi"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"北村 嘉章"},{"name":"近藤 勇人"},{"name":"黒田 若奈"},{"name":"吉田 陽香"},{"name":"宮本 裕子"},{"name":"服部 将史"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H1 receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene.","ja":"Therapeutics targeting disease-sensitive genes are required for the therapy of multifactorial diseases. There is no clinical report on therapeutics for allergic disease-sensitive genes. We are focusing on the histamine H1 receptor (H1R) as a sensitive gene. H1R mediates allergy histamine signals. H1R is a rate-limiting molecule of the H1R signal because the signal is increased with elevated receptor expression level. We discovered that the stimulation of H1R induced H1R gene expression through PKCδ activation, resulting in receptor upregulation. The mechanism of H1R gene expression was revealed to play a key role in the receptor expression level in studies using cultured HeLa cells and allergic rhinitis model rats. Preseasonal prophylactic treatment with antihistamines is recommended for the therapy of pollinosis. However, the mechanism of the therapy remains to be elucidated. We demonstrated that repeated pretreatment treatment with antihistamines in the allergic rhinitis model rats resulted not only in improvement of symptoms but also in suppressed elevation of H1R mRNA levels in the nasal mucosa. A clinical trial was then initiated. When symptoms and H1R mRNA levels in the nasal mucosa of pollinosis patients with or without preseasonal prophylactic treatment with antihistamines were examined, both symptoms and high levels of H1R mRNA were significantly improved in treated compared with untreated patients. These results strongly suggest that H1R is an allergic disease-sensitive gene."},"publication_date":"2011-02","publication_name":{"en":"Journal of the Pharmaceutical Society of Japan","ja":"薬学雑誌"},"volume":"Vol.131","number":"No.2","starting_page":"171","ending_page":"178","languages":["jpn"],"referee":true,"identifiers":{"doi":["10.1248/yakushi.131.171"],"issn":["0031-6903"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21225009","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=234711","label":"url"}],"paper_title":{"en":"Innervation of histamine neurons in the caudal part of the arcuate nucleus of hypothalamus and their activation in response to food deprivation under scheduled feeding.","ja":"Innervation of histamine neurons in the caudal part of the arcuate nucleus of hypothalamus and their activation in response to food deprivation under scheduled feeding."},"authors":{"en":[{"name":"Umehara Hayato"},{"name":"Mizuguchi Hiroyuki"},{"name":"Mizukawa N"},{"name":"Matsumoto M"},{"name":"Takeda Noriaki"},{"name":"Senba E"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"梅原 隼人"},{"name":"水口 博之"},{"name":"Mizukawa N"},{"name":"Matsumoto M"},{"name":"武田 憲昭"},{"name":"Senba E"},{"name":"福井 裕行"}]},"description":{"en":"It has been well established that histaminergic neurons innervate densely the anterior hypothalamus and regulate several functions through the histamine H receptor (H1R). However, the physiological function of the histaminergic neurons in other regions including the posterior hypothalamus has not been fully investigated. Recently, we have found a selective c-Fos expression in the caudal part of the arcuate nucleus of the hypothalamus (cARC) by food deprivation under scheduled feeding in rats. In this study, we histochemically examined the correlation of this c-Fos expression with the activation of histaminergic neurons in this region using an anti-H1R antibody. Strong H1R immunoreactivity was observed in the perikarya of the c-Fos positive cells. Abundant histamine-containing fibers were also found in the cARC and in the area between the cARC and the tuberomammillary nucleus (TM), where the histaminergic neuronal cell bodies are exclusively distributed. Our morphological observations suggest that c-Fos expression in the cARC by food deprivation under scheduled feeding is caused by the activation of histaminergic neurons projected from the TM.","ja":"It has been well established that histaminergic neurons innervate densely the anterior hypothalamus and regulate several functions through the histamine H receptor (H1R). However, the physiological function of the histaminergic neurons in other regions including the posterior hypothalamus has not been fully investigated. Recently, we have found a selective c-Fos expression in the caudal part of the arcuate nucleus of the hypothalamus (cARC) by food deprivation under scheduled feeding in rats. In this study, we histochemically examined the correlation of this c-Fos expression with the activation of histaminergic neurons in this region using an anti-H1R antibody. Strong H1R immunoreactivity was observed in the perikarya of the c-Fos positive cells. Abundant histamine-containing fibers were also found in the cARC and in the area between the cARC and the tuberomammillary nucleus (TM), where the histaminergic neuronal cell bodies are exclusively distributed. Our morphological observations suggest that c-Fos expression in the cARC by food deprivation under scheduled feeding is caused by the activation of histaminergic neurons projected from the TM."},"publication_date":"2010-12","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.32","number":"No.10","starting_page":"733","ending_page":"736","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2010.32.10.1545781"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21225011","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=231981","label":"url"}],"paper_title":{"en":"Preseasonal prophylactic treatment with antihistamines suppresses nasal symptoms and expression of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis.","ja":"Preseasonal prophylactic treatment with antihistamines suppresses nasal symptoms and expression of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Kitamura Yoshiaki"},{"name":"Kondo Y"},{"name":"Kuroda W"},{"name":"Yoshida H"},{"name":"Miyamoto Y"},{"name":"Hattori M"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"水口 博之"},{"name":"北村 嘉章"},{"name":"Kondo Y"},{"name":"Kuroda W"},{"name":"Yoshida H"},{"name":"Miyamoto Y"},{"name":"Hattori M"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"Administration of antihistamines 2-4 weeks before the pollen season showed a greater inhibitory effect on nasal allergy symptoms in patients with seasonal allergic rhinitis. However, the mechanism of slow-onset effects of preseasonal treatment with antihistamines remains unclear. Here, we investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of histamine H₁ receptor (H1R) mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. Moreover, there was a significant correlation between the nasal symptoms and the expression of H1R mRNA in both patients with or without preseasonal prophylactic treatment. These findings suggest that preseasonal prophylactic treatment with antihistamines is more effective than on-seasonal administration to patients with pollinosis in reducing nasal symptoms during the peak pollen period by suppressing H1R gene expression in the nasal mucosa.","ja":"Administration of antihistamines 2-4 weeks before the pollen season showed a greater inhibitory effect on nasal allergy symptoms in patients with seasonal allergic rhinitis. However, the mechanism of slow-onset effects of preseasonal treatment with antihistamines remains unclear. Here, we investigated the effect of preseasonal prophylactic treatment with antihistamines on nasal symptoms and the expression of histamine H₁ receptor (H1R) mRNA of the nasal mucosa in patients with cedar pollen pollinosis. During the peak pollen period, the expression of H1R mRNA in the nasal mucosa and the scores of sneezing and watery rhinorrhea in patients receiving preseasonal prophylactic treatment with antihistamines were significantly suppressed in comparison with those in the patients without treatment. Moreover, there was a significant correlation between the nasal symptoms and the expression of H1R mRNA in both patients with or without preseasonal prophylactic treatment. These findings suggest that preseasonal prophylactic treatment with antihistamines is more effective than on-seasonal administration to patients with pollinosis in reducing nasal symptoms during the peak pollen period by suppressing H1R gene expression in the nasal mucosa."},"publication_date":"2010-12","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.32","number":"No.10","starting_page":"745","ending_page":"748","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2010.32.10.1533687"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20818926","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=234707","label":"url"}],"paper_title":{"en":"Potential of Baliospermum montanum against compound 48/80-induced systemic anaphylaxis.","ja":"Potential of Baliospermum montanum against compound 48/80-induced systemic anaphylaxis."},"authors":{"en":[{"name":"Venkatesh P"},{"name":"Mukherjee PK"},{"name":"Mukherjee D"},{"name":"Bandyopadhyay A"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"}],"ja":[{"name":"Venkatesh P"},{"name":"Mukherjee PK"},{"name":"Mukherjee D"},{"name":"Bandyopadhyay A"},{"name":"福井 裕行"},{"name":"水口 博之"}]},"description":{"en":"Decoctions of Baliospermum montanum Müll. Arg. (Euphorbiaceae) leaves are reported to be useful in the treatment of asthma and other respiratory complications in the Ayurvedic system. Objective: To evaluate the mast cell stabilization and antihistaminic activities of the chloroform (BMLC) and ethanol (BMLE) extracts of the leaves of Baliospermum montanum. The stabilization potential was studied on mouse peritoneal mast cells and the antihistaminic activity was carried out by determining the mortality rate of mice treated with toxicant (compound 48/80) and the effect on elevation of histamine release upon degranulation. The increased number of intact mast cells (43.640 ± 1.7% and 61.57 ± 1.79% at 200 and 400 mg/ kg, respectively) suggested that the BMLC stabilized the mast cell degranulation and showed decreased elevation of histamine. BMLC extract was found to be most effective against degranulation and release of histamine from mast cells. Identifying the lead from this plant will be a definite target for treating allergic diseases.","ja":"Decoctions of Baliospermum montanum Müll. Arg. (Euphorbiaceae) leaves are reported to be useful in the treatment of asthma and other respiratory complications in the Ayurvedic system. Objective: To evaluate the mast cell stabilization and antihistaminic activities of the chloroform (BMLC) and ethanol (BMLE) extracts of the leaves of Baliospermum montanum. The stabilization potential was studied on mouse peritoneal mast cells and the antihistaminic activity was carried out by determining the mortality rate of mice treated with toxicant (compound 48/80) and the effect on elevation of histamine release upon degranulation. The increased number of intact mast cells (43.640 ± 1.7% and 61.57 ± 1.79% at 200 and 400 mg/ kg, respectively) suggested that the BMLC stabilized the mast cell degranulation and showed decreased elevation of histamine. BMLC extract was found to be most effective against degranulation and release of histamine from mast cells. Identifying the lead from this plant will be a definite target for treating allergic diseases."},"publication_date":"2010-09-06","publication_name":{"en":"Pharmaceutical Biology","ja":"Pharmaceutical Biology"},"volume":"Vol.48","number":"No.11","starting_page":"1213","ending_page":"1217","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3109/13880201003677827"],"issn":["1744-5116"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=224267","label":"url"}],"paper_title":{"en":"スギ花粉症における初期療法の作用機序の検討","ja":"スギ花粉症における初期療法の作用機序の検討"},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"黒田 若奈"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"黒田 若奈"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"publication_date":"2010-07","publication_name":{"en":"Japanese Journal of Rhinology","ja":"日本鼻科学会会誌"},"volume":"Vol.49","number":"No.3","starting_page":"375","ending_page":"375","languages":["jpn"],"referee":true,"identifiers":{"issn":["0910-9153"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20236220","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212507","label":"url"}],"paper_title":{"en":"Ubiquitin/proteasome-dependent down-regulation following clathrin-mediated internalization of histamine H1-receptors in Chinese hamster ovary cells.","ja":"Ubiquitin/proteasome-dependent down-regulation following clathrin-mediated internalization of histamine H1-receptors in Chinese hamster ovary cells."},"authors":{"en":[{"name":"Hishinuma Shigeru"},{"name":"Komazaki Hiroshi"},{"name":"Fukui Hiroyuki"},{"name":"Shoji Masaru"}],"ja":[{"name":"Hishinuma Shigeru"},{"name":"Komazaki Hiroshi"},{"name":"福井 裕行"},{"name":"Shoji Masaru"}]},"description":{"en":"We investigated the regulatory pathways responsible for agonist-induced internalization and down-regulation of G(q) protein-coupled histamine H(1)-receptors in Chinese hamster ovary cells. Histamine-induced internalization and down-regulation of H(1)-receptors were detected as the loss of [(3)H]mepyramine binding sites on intact cells accessible to hydrophilic and hydrophobic H(1)-receptor antagonists, pirdonium and mepyramine, respectively. Pretreatment of cells with 0.1 mM histamine for 30 min at 37 degrees C induced internalization as well as down-regulation of H(1)-receptors, both of which were inhibited either in the presence of an inhibitor against G protein-coupled receptor kinases (ZnCl(2)) or under hypertonic conditions where clathrin-dependent endocytosis is known to be inhibited, but were not affected by inhibitors against caveolae/raft-dependent endocytosis (filipin and nystatin). Down-regulation of H(1)-receptors, but not their internalization, was inhibited by protein kinase C inhibitors (chelerythrin or GF109203X), a ubiquitin E1 inhibitor (UBEI-41) and proteasome inhibitors (lactacystin and MG-132). Neither a Ca(2+)/calmodulin-dependent protein kinase II inhibitor (KN-62) nor lysosomal protease inhibitors (E-64, leupeptin, chloroquine and NH(4)Cl) affected the internalization and down-regulation of H(1)-receptors. These results suggest that H(1)-receptors internalize upon agonist stimulation via G protein-coupled receptor kinase/clathrin-dependent but caveolae/raft-independent mechanisms and are delivered to proteasomes, preferentially to lysosomes, for their prompt down-regulation.","ja":"We investigated the regulatory pathways responsible for agonist-induced internalization and down-regulation of G(q) protein-coupled histamine H(1)-receptors in Chinese hamster ovary cells. Histamine-induced internalization and down-regulation of H(1)-receptors were detected as the loss of [(3)H]mepyramine binding sites on intact cells accessible to hydrophilic and hydrophobic H(1)-receptor antagonists, pirdonium and mepyramine, respectively. Pretreatment of cells with 0.1 mM histamine for 30 min at 37 degrees C induced internalization as well as down-regulation of H(1)-receptors, both of which were inhibited either in the presence of an inhibitor against G protein-coupled receptor kinases (ZnCl(2)) or under hypertonic conditions where clathrin-dependent endocytosis is known to be inhibited, but were not affected by inhibitors against caveolae/raft-dependent endocytosis (filipin and nystatin). Down-regulation of H(1)-receptors, but not their internalization, was inhibited by protein kinase C inhibitors (chelerythrin or GF109203X), a ubiquitin E1 inhibitor (UBEI-41) and proteasome inhibitors (lactacystin and MG-132). Neither a Ca(2+)/calmodulin-dependent protein kinase II inhibitor (KN-62) nor lysosomal protease inhibitors (E-64, leupeptin, chloroquine and NH(4)Cl) affected the internalization and down-regulation of H(1)-receptors. These results suggest that H(1)-receptors internalize upon agonist stimulation via G protein-coupled receptor kinase/clathrin-dependent but caveolae/raft-independent mechanisms and are delivered to proteasomes, preferentially to lysosomes, for their prompt down-regulation."},"publication_date":"2010-03-04","publication_name":{"en":"Journal of Neurochemistry","ja":"Journal of Neurochemistry"},"volume":"Vol.113","number":"No.4","starting_page":"990","ending_page":"1001","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/j.1471-4159.2010.06669.x"],"issn":["1471-4159"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20109037","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212509","label":"url"}],"paper_title":{"en":"Anti-allergic activity of standardized extract of Albizia lebbeck with reference to catechin as a phytomarker.","ja":"Anti-allergic activity of standardized extract of Albizia lebbeck with reference to catechin as a phytomarker."},"authors":{"en":[{"name":"Venkatesh Pichairajan"},{"name":"Mukherjee Pulok K"},{"name":"Kumar Nanjappan Satheesh"},{"name":"Bandyopadhyay Arun"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Islam Nurul"}],"ja":[{"name":"Venkatesh Pichairajan"},{"name":"Mukherjee Pulok K"},{"name":"Kumar Nanjappan Satheesh"},{"name":"Bandyopadhyay Arun"},{"name":"福井 裕行"},{"name":"水口 博之"},{"name":"Islam Nurul"}]},"description":{"en":"BACKGROUND AND AIM: The major groups of phytonutrients found in plants include polyphenols, flavonoids, terpenes, amines, etc., all of which are observed to have potential anti-allergic activity. In this study, we evaluated the anti-allergic activity of the standardized extract of Albizia lebbeck with respect to the catechin, a polyphenolic phytomarker. MATERIAL AND METHODS: The percentage of catechin in the ethanolic extract was found to be 14.72 mg/g. We administered Albizia lebbeck (50-300 mg/kg) and 50 mg/kg of catechin to mice to evaluate the mast cell stabilization and estimation of histamine elevation in the plasma. RESULTS AND CONCLUSION: Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC(50) value of Albizia lebbeck was found to be 85 microg/ml. This inhibitory potential of catechin from Albizia lebbeck is perhaps due to modulation of two important effector's functions, histamine release and cytokine expression of antigen -IgE activated mast cells.","ja":"BACKGROUND AND AIM: The major groups of phytonutrients found in plants include polyphenols, flavonoids, terpenes, amines, etc., all of which are observed to have potential anti-allergic activity. In this study, we evaluated the anti-allergic activity of the standardized extract of Albizia lebbeck with respect to the catechin, a polyphenolic phytomarker. MATERIAL AND METHODS: The percentage of catechin in the ethanolic extract was found to be 14.72 mg/g. We administered Albizia lebbeck (50-300 mg/kg) and 50 mg/kg of catechin to mice to evaluate the mast cell stabilization and estimation of histamine elevation in the plasma. RESULTS AND CONCLUSION: Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC(50) value of Albizia lebbeck was found to be 85 microg/ml. This inhibitory potential of catechin from Albizia lebbeck is perhaps due to modulation of two important effector's functions, histamine release and cytokine expression of antigen -IgE activated mast cells."},"publication_date":"2010-02","publication_name":{"en":"Immunopharmacology and Immunotoxicology","ja":"Immunopharmacology and Immunotoxicology"},"volume":"Vol.32","number":"No.2","starting_page":"272","ending_page":"276","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3109/08923970903305481"],"issn":["1532-2513"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20112007","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212508","label":"url"}],"paper_title":{"en":"Interleukin-4 up-regulates histamine H1 receptors by activation of H1 receptor gene transcription.","ja":"Interleukin-4 up-regulates histamine H1 receptors by activation of H1 receptor gene transcription."},"authors":{"en":[{"name":"Horio Shuhei"},{"name":"Fujimoto Katsumi"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"堀尾 修平"},{"name":"Fujimoto Katsumi"},{"name":"水口 博之"},{"name":"福井 裕行"}]},"description":{"en":"Histamine plays an important role in allergy mainly through histamine H1 receptor (H1R). Recent studies showed that the H1R level is elevated in allergic conditions, suggesting that this will make the allergic symptoms worse by intensifying H1R-mediated processes. Some cytokines are also involved in allergy, and interleukin-4 (IL-4) has been implicated as an important mediator of allergic inflammation. It is noteworthy that the level of IL-4 is elevated under allergic states. We tested whether IL-4 has a role in up-regulating H1R level by using the cultured human HeLa cell as a model system that expresses both IL-4 receptor and H1R. IL-4 stimulation increased H1R protein levels and H1R mRNA levels. IL-4 also increased H1R promoter activity, but had no effect on H1R mRNA stability, indicating that up-regulation of H1R was due to an increase in H1R mRNA synthesis. IL-4 activated STAT6 (signal transducer and activator of transcription 6) in HeLa cells, and up-regulation of H1R mRNA and activation of STAT6 by IL-4 were inhibited by a specific JAK3 (Janus-activated kinase 3) inhibitor. Stimulation with histamine also up-regulated H1R mRNA, and co-stimulation with histamine and IL-4 elevated H1R mRNA level significantly higher than the stimulation with histamine or IL-4 alone did. These results indicated that IL-4 up-regulated H1R mRNA level through increased transcription of H1R gene via JAK3-STAT6 pathway. The effects of histamine and IL-4 were additive, suggesting that these allergic mediators will work together to up-regulate H1R level, and thus make the allergic symptom worse by intensifying H1R-mediated allergic processes.","ja":"Histamine plays an important role in allergy mainly through histamine H1 receptor (H1R). Recent studies showed that the H1R level is elevated in allergic conditions, suggesting that this will make the allergic symptoms worse by intensifying H1R-mediated processes. Some cytokines are also involved in allergy, and interleukin-4 (IL-4) has been implicated as an important mediator of allergic inflammation. It is noteworthy that the level of IL-4 is elevated under allergic states. We tested whether IL-4 has a role in up-regulating H1R level by using the cultured human HeLa cell as a model system that expresses both IL-4 receptor and H1R. IL-4 stimulation increased H1R protein levels and H1R mRNA levels. IL-4 also increased H1R promoter activity, but had no effect on H1R mRNA stability, indicating that up-regulation of H1R was due to an increase in H1R mRNA synthesis. IL-4 activated STAT6 (signal transducer and activator of transcription 6) in HeLa cells, and up-regulation of H1R mRNA and activation of STAT6 by IL-4 were inhibited by a specific JAK3 (Janus-activated kinase 3) inhibitor. Stimulation with histamine also up-regulated H1R mRNA, and co-stimulation with histamine and IL-4 elevated H1R mRNA level significantly higher than the stimulation with histamine or IL-4 alone did. These results indicated that IL-4 up-regulated H1R mRNA level through increased transcription of H1R gene via JAK3-STAT6 pathway. The effects of histamine and IL-4 were additive, suggesting that these allergic mediators will work together to up-regulate H1R level, and thus make the allergic symptom worse by intensifying H1R-mediated allergic processes."},"publication_date":"2010-01-30","publication_name":{"en":"Naunyn-Schmiedeberg's Archives of Pharmacology","ja":"Naunyn-Schmiedeberg's Archives of Pharmacology"},"volume":"Vol.381","number":"No.4","starting_page":"305","ending_page":"313","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00210-010-0491-z"],"issn":["1432-1912"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19050374","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212512","label":"url"}],"paper_title":{"en":"Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats.","ja":"Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats."},"authors":{"en":[{"name":"Das Asish Kumar"},{"name":"Mizuguchi Hiroyuki"},{"name":"Kodama Madoka"},{"name":"Dev Shrabanti"},{"name":"Umehara Hayato"},{"name":"Kitamura Yoshiaki"},{"name":"Matsushita Chiyo"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Das Asish Kumar"},{"name":"水口 博之"},{"name":"Kodama Madoka"},{"name":"Dev Shrabanti"},{"name":"梅原 隼人"},{"name":"北村 嘉章"},{"name":"Matsushita Chiyo"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"BACKGROUND: The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats. METHODS: Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 microl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR. RESULTS: SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13. CONCLUSIONS: These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases.","ja":"BACKGROUND: The therapeutic use of Kampo medicine, Sho-seiryu-to (SST) in allergic disorders is well known. As histamine plays a central role in allergic diseases, it is possible that SST affects the allergy-related histamine signaling. In this study, we investigated the effect of SST on allergy-related histamine signaling in the nasal mucosa of toluene 2, 4-diisocyanate (TDI)-sensitized nasal allergy model rats. METHODS: Six-week-old male, Brown Norway rats were sensitized for 2 weeks with 10 microl of 10% TDI, and after a 1 week interval, provocation was initiated with the same amount of TDI. SST (0.6g/rat) was given orally 1 hour before TDI treatment began for a period of 3 weeks. Nasal symptoms were scored for 10 minutes immediately after TDI-provocation. The genes expression in nasal mucosa was determined using real-time quantitative RT-PCR. RESULTS: SST significantly suppressed TDI-induced nasal allergy-like symptoms. TDI provocation showed a significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) gene expressions. Prolonged pre-treatment of SST significantly suppressed the mRNA levels of H1R and HDC that was up-regulated by TDI. SST also suppressed TDI-induced interleukin (IL)-4 and IL-5 mRNA elevation. However, SST showed no significant effect for TDI-induced mRNA elevation of IL-13. CONCLUSIONS: These results demonstrate that SST alleviates nasal symptoms by the inhibition of histamine signaling through suppression of TDI-induced H1R and HDC gene up-regulation. SST also suppresses cytokine signaling through suppression of IL-4 and IL-5 gene expression. Suppression of histamine signaling may be a novel mechanism of SST in preventing allergic diseases."},"publication_date":"2009-12-01","publication_name":{"en":"Allergology International","ja":"Allergology International"},"volume":"Vol.58","number":"No.1","starting_page":"81","ending_page":"88","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2332/allergolint.O-07-526"],"issn":["1323-8930"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19781614","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212505","label":"url"}],"paper_title":{"en":"Mast cell stabilization and antihistaminic potentials of Curculigo orchioides rhizomes.","ja":"Mast cell stabilization and antihistaminic potentials of Curculigo orchioides rhizomes."},"authors":{"en":[{"name":"Venkatesh P"},{"name":"Mukherjee Pulok K"},{"name":"Kumar Satheesh N"},{"name":"Nema Neelesh K"},{"name":"Bandyopadhyay A"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"}],"ja":[{"name":"Venkatesh P"},{"name":"Mukherjee Pulok K"},{"name":"Kumar Satheesh N"},{"name":"Nema Neelesh K"},{"name":"Bandyopadhyay A"},{"name":"福井 裕行"},{"name":"水口 博之"}]},"description":{"en":"AIM OF THE STUDY: To investigate the mast cell stabilization and antihistaminic activities of the rhizomes of Curculigo orchioides (COR). Extract of Curculigo orchioides Gaertn. (Fam. Amaryllidaceae) has been reported to possess immunostimulant, and anti-inflammatory potentials. In Indian traditional system of medicine it is also used as anti-asthmatic and anti-inflammatory. MATERIALS AND METHODS: Estimation of histamine release is key parameter for evaluating any target for its anti-allergic potential. The stabilization potential of the alcoholic extract of COR (100-400mg/kg) against mast cell degranulation was studied on isolated mice peritoneal mast cells. The antihistaminic activity was performed by determining the mortality rate of mice upon exposure to compound 48/80 and effect on inhibition of histamine release upon degranulation. RESULTS: The raised number of intact mast cells intimates that the COR stabilized the mast cell degranulation (60.96+/-1.96%) and percentage antihistaminic potential of the extract (63.58+/-1.8 inhibition at dose of 400mg/kg) and it virtues further work towards the isolation of phytoconstituents from this plant. CONCLUSION: This finding provides evidence that COR inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation.","ja":"AIM OF THE STUDY: To investigate the mast cell stabilization and antihistaminic activities of the rhizomes of Curculigo orchioides (COR). Extract of Curculigo orchioides Gaertn. (Fam. Amaryllidaceae) has been reported to possess immunostimulant, and anti-inflammatory potentials. In Indian traditional system of medicine it is also used as anti-asthmatic and anti-inflammatory. MATERIALS AND METHODS: Estimation of histamine release is key parameter for evaluating any target for its anti-allergic potential. The stabilization potential of the alcoholic extract of COR (100-400mg/kg) against mast cell degranulation was studied on isolated mice peritoneal mast cells. The antihistaminic activity was performed by determining the mortality rate of mice upon exposure to compound 48/80 and effect on inhibition of histamine release upon degranulation. RESULTS: The raised number of intact mast cells intimates that the COR stabilized the mast cell degranulation (60.96+/-1.96%) and percentage antihistaminic potential of the extract (63.58+/-1.8 inhibition at dose of 400mg/kg) and it virtues further work towards the isolation of phytoconstituents from this plant. CONCLUSION: This finding provides evidence that COR inhibits mast cell-derived immediate-type allergic reactions and mast cell degranulation."},"publication_date":"2009-09-23","publication_name":{"en":"Journal of Ethnopharmacology","ja":"Journal of Ethnopharmacology"},"volume":"Vol.126","number":"No.3","starting_page":"434","ending_page":"436","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jep.2009.09.019"],"issn":["1872-7573"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19596986","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212514","label":"url"}],"paper_title":{"en":"Suplatast tosilate inhibits histamine signaling by direct and indirect down-regulation of histamine H1 receptor gene expression through suppression of histidine decarboxylase and IL-4 gene transcriptions.","ja":"Suplatast tosilate inhibits histamine signaling by direct and indirect down-regulation of histamine H1 receptor gene expression through suppression of histidine decarboxylase and IL-4 gene transcriptions."},"authors":{"en":[{"name":"Shahriar Masum"},{"name":"Mizuguchi Hiroyuki"},{"name":"Maeyama Kazutaka"},{"name":"Kitamura Yoshiaki"},{"name":"Orimoto Naoki"},{"name":"Horio Shuhei"},{"name":"Umehara Hayato"},{"name":"Hattori Masashi"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Shahriar Masum"},{"name":"水口 博之"},{"name":"Maeyama Kazutaka"},{"name":"北村 嘉章"},{"name":"Orimoto Naoki"},{"name":"堀尾 修平"},{"name":"梅原 隼人"},{"name":"Hattori Masashi"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively.","ja":"Allergic rhinitis (AR) is an inflammatory disorder typified by symptoms such as sneezing, congestion, and rhinorrhea. Histamine plays important roles in eliciting AR symptoms. Up-regulation of the histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNAs was observed in AR patients. Th2 cytokines are also involved in the pathogenesis of AR. We examined the effect of suplatast tosilate on nasal symptoms, and H1R, HDC, and IL-4 gene expression using toluene-2,4-diisocyanate (TDI)-sensitized rats and HeLa cells expressing endogenous H1R. Provocation with TDI increased nasal symptoms, HDC activity, the histamine content of nasal lavage fluid, and the expression of H1R, HDC, and IL-4 mRNAs in TDI-sensitized rats. Pretreatment with suplatast for 2 wk significantly suppressed TDI-induced nasal symptoms and elevation of H1R, HDC, and IL-4 mRNAs. Suplatast also suppressed HDC activity in the nasal mucosa and the histamine content of the nasal lavage fluid. Bilateral injection of IL-4 into the nasal cavity of normal rats up-regulated H1R mRNA, while intranasal application of histamine up-regulated IL-4 mRNA. Suplatast suppressed IL-4-induced up-regulation of H1R mRNA in HeLa cells. However, it did not inhibit histamine-induced H1R mRNA elevation. These results suggest that suplatast alleviates nasal symptoms by inhibiting histamine signaling in TDI-sensitized rats through the suppression of histamine- and IL-4-induced H1R gene expression by the inhibitions of HDC and IL-4 gene transcriptions, respectively."},"publication_date":"2009-07-13","publication_name":{"en":"The Journal of Immunology","ja":"The Journal of Immunology"},"volume":"Vol.183","number":"No.3","starting_page":"2133","ending_page":"2141","languages":["eng"],"referee":true,"identifiers":{"doi":["10.4049/jimmunol.0901058"],"issn":["1550-6606"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19352071","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212504","label":"url"}],"paper_title":{"en":"Kujin suppresses histamine signaling at the transcriptional level in toluene 2,4-diisocyanate-sensitized rats.","ja":"Kujin suppresses histamine signaling at the transcriptional level in toluene 2,4-diisocyanate-sensitized rats."},"authors":{"en":[{"name":"Dev Shrabanti"},{"name":"Mizuguchi Hiroyuki"},{"name":"Das Asish K"},{"name":"Maeyama Kazutaka"},{"name":"Horinaga Shiho"},{"name":"Kato Shuhei"},{"name":"Tamada Misaki"},{"name":"Hattori Masashi"},{"name":"Umehara Hayato"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Dev Shrabanti"},{"name":"水口 博之"},{"name":"Das Asish K"},{"name":"Maeyama Kazutaka"},{"name":"Horinaga Shiho"},{"name":"Kato Shuhei"},{"name":"Tamada Misaki"},{"name":"Hattori Masashi"},{"name":"梅原 隼人"},{"name":"福井 裕行"}]},"description":{"en":"Kujin, the dried root of Sophorae flavescensis, has been used in Chinese folklore medicine against allergy. Evaluation of its anti-allergic potential as well as its mechanism of action has rarely been established. We investigated the effect of Kujin on toluene-2,4-diisocyanate (TDI)-induced allergic behavior and related histamine signaling including mRNA levels of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC), H1R and HDC activities, and histamine content in rat nasal mucosa. We also investigated the effect of Kujin on the mRNA levels of helper T cell type 2 (Th2)-cytokine genes closely related to histamine signaling. TDI provocation caused acute allergic symptoms accompanied with up-regulations of H1R and HDC mRNAs and increases in HDC activity, histamine content, and [(3)H]mepyramine binding activity in the nasal mucosa, all of which were significantly suppressed by pretreatment with Kujin for 3 weeks. Kujin also suppressed the TDI-induced IL-4 and IL-5 mRNA elevations. These data suggest that oral administration of Kujin showed anti-allergic activity through suppression of histamine signaling by the inhibition of TDI-induced H1R and HDC mRNA elevations followed by decrease in H1R, HDC protein level, and histamine content in the nasal mucosa of TDI-sensitized rats. Suppression of Th2-cytokine signaling by Kujin also suggests that it could affect the histamine-cytokine network.","ja":"Kujin, the dried root of Sophorae flavescensis, has been used in Chinese folklore medicine against allergy. Evaluation of its anti-allergic potential as well as its mechanism of action has rarely been established. We investigated the effect of Kujin on toluene-2,4-diisocyanate (TDI)-induced allergic behavior and related histamine signaling including mRNA levels of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC), H1R and HDC activities, and histamine content in rat nasal mucosa. We also investigated the effect of Kujin on the mRNA levels of helper T cell type 2 (Th2)-cytokine genes closely related to histamine signaling. TDI provocation caused acute allergic symptoms accompanied with up-regulations of H1R and HDC mRNAs and increases in HDC activity, histamine content, and [(3)H]mepyramine binding activity in the nasal mucosa, all of which were significantly suppressed by pretreatment with Kujin for 3 weeks. Kujin also suppressed the TDI-induced IL-4 and IL-5 mRNA elevations. These data suggest that oral administration of Kujin showed anti-allergic activity through suppression of histamine signaling by the inhibition of TDI-induced H1R and HDC mRNA elevations followed by decrease in H1R, HDC protein level, and histamine content in the nasal mucosa of TDI-sensitized rats. Suppression of Th2-cytokine signaling by Kujin also suggests that it could affect the histamine-cytokine network."},"publication_date":"2009-04-07","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.109","number":"No.4","starting_page":"606","ending_page":"617","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.09003FP"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18607976","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=201710","label":"url"}],"paper_title":{"en":"Effects of hypergravity on histamine H1 receptor mRNA expression in hypothalamus and brainstem of rats: implications for development of motion sickness","ja":"Effects of hypergravity on histamine H1 receptor mRNA expression in hypothalamus and brainstem of rats: implications for development of motion sickness"},"authors":{"en":[{"name":"Satou Gou"},{"name":"Uno Atsuhiko"},{"name":"Horii Arata"},{"name":"Umehara Hayato"},{"name":"Kitamura Yoshiaki"},{"name":"Sekine Kazunori"},{"name":"Tamura Koichi"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"佐藤 豪"},{"name":"Uno Atsuhiko"},{"name":"Horii Arata"},{"name":"梅原 隼人"},{"name":"北村 嘉章"},{"name":"関根 和教"},{"name":"田村 公一"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.","ja":"The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats."},"publication_date":"2009-01","publication_name":{"en":"Acta Oto-Laryngologica","ja":"Acta Oto-Laryngologica"},"volume":"Vol.129","number":"No.1","starting_page":"45","ending_page":"51","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/00016480802008173"],"issn":["1651-2251"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19075512","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212513","label":"url"}],"paper_title":{"en":"Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.","ja":"Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Hatano Masaya"},{"name":"Matsushita Chiyo"},{"name":"Umehara Hayato"},{"name":"Kuroda Wakana"},{"name":"Kitamura Yoshiyuki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Hatano Masaya"},{"name":"Matsushita Chiyo"},{"name":"梅原 隼人"},{"name":"Kuroda Wakana"},{"name":"Kitamura Yoshiyuki"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa.","ja":"Antihistamines are effective for treatment of seasonal nasal allergy. Recently, prophylactic treatment with antihistamines in patients with pollinosis was reported to be more effective when started before the pollen season. The administration with antihistamines from 2 to 6 weeks before onset of the pollen season is recommended for management of allergic rhinitis in Japan. To determine the reason for the effectiveness of prophylactic treatment with antihistamines, the effects of repeated pre-treatment with antihistamines before provocation with toluene 2,4-diisocyanate (TDI) on their nasal allergy-like behavior and up-regulations of histamine H(1) receptors (H1R) and interleukin (IL)-4 mRNAs in their nasal mucosa were examined. Provocation with TDI induced sneezing and up-regulations of H1R and IL-4 mRNAs in the nasal mucosa of TDI-sensitized rats. Repeated pre-treatments with antihistamines including epinastine, olopatadine, or d-chlorpheniramine for 1 to 5 weeks before provocation with TDI suppressed TDI-induced sneezing and the up-regulations of H1R and IL-4 mRNAs in the nasal mucosa more than their administrations once or for 3 days before TDI provocation. Our data indicate that repeated pre-treatment with antihistamines before provocation with TDI is more effective than their single treatment in reducing nasal allergy-like behavior by causing additional suppression of up-regulations of H1R and IL-4 mRNAs in the nasal mucosa."},"publication_date":"2008-12-10","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.108","number":"No.4","starting_page":"480","ending_page":"486","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.08222FP"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18566547","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212511","label":"url"}],"paper_title":{"en":"Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).","ja":"Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS)."},"authors":{"en":[{"name":"Izumi Norimasa"},{"name":"Mizuguchi Hiroyuki"},{"name":"Umehara Hayato"},{"name":"Ogino Satoshi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Izumi Norimasa"},{"name":"水口 博之"},{"name":"梅原 隼人"},{"name":"Ogino Satoshi"},{"name":"福井 裕行"}]},"description":{"en":"BACKGROUND: H(1) antihistamines are widely used as therapeutics for allergic diseases. Sedation is a well-known side effect of H(1) antihistamines and sometimes it is life-threatening for patients. Thus it is important to evaluate the sedative properties of H(1) antihistamines to avoid side effects. For this purpose, histamine H(1) receptor (H1R) occupancy and proportional impairment ratios (PIR) are now being used. However, it is not easy to obtain these parameters. Here, we sought to evaluate the sedative properties of H(1) antihistamines by means of a large-scale surveillance at health insurance pharmacies. METHODS: The survey was conducted at 37 health insurance pharmacies. The therapeutic efficacy and the degree of sleepiness were quantified through a questionnaire using the visual analog scale (VAS) directly from 1742 patients who received H(1) antihistamines. RESULTS: The degree of sleepiness caused by the first-generation antihistamines was significantly higher than that of the second-generation antihistamines. The high VAS score in case of efficacy was found in d-chlorpheniramine, olopatadine, and ebastine. Among the mean values of efficacy, all second-generation antihistamines except for loratadine, bepotastine, and mequitazine were significantly higher than that of clemastine. Regarding the degree of sleepiness, clemastine scored the highest VAS score, and significantly lower scores were obtained in all second-generation antihistamines. CONCLUSIONS: The sedative properties of the H(1) antihistamines obtained from VAS analysis were very similar to those of H1R occupancy from positron emission tomography (PET) studies and PIR from meta-analysis. Our results indicate that large-scale surveillance using VAS might be useful to evaluate the profiles of H(1) antihistamines.","ja":"BACKGROUND: H(1) antihistamines are widely used as therapeutics for allergic diseases. Sedation is a well-known side effect of H(1) antihistamines and sometimes it is life-threatening for patients. Thus it is important to evaluate the sedative properties of H(1) antihistamines to avoid side effects. For this purpose, histamine H(1) receptor (H1R) occupancy and proportional impairment ratios (PIR) are now being used. However, it is not easy to obtain these parameters. Here, we sought to evaluate the sedative properties of H(1) antihistamines by means of a large-scale surveillance at health insurance pharmacies. METHODS: The survey was conducted at 37 health insurance pharmacies. The therapeutic efficacy and the degree of sleepiness were quantified through a questionnaire using the visual analog scale (VAS) directly from 1742 patients who received H(1) antihistamines. RESULTS: The degree of sleepiness caused by the first-generation antihistamines was significantly higher than that of the second-generation antihistamines. The high VAS score in case of efficacy was found in d-chlorpheniramine, olopatadine, and ebastine. Among the mean values of efficacy, all second-generation antihistamines except for loratadine, bepotastine, and mequitazine were significantly higher than that of clemastine. Regarding the degree of sleepiness, clemastine scored the highest VAS score, and significantly lower scores were obtained in all second-generation antihistamines. CONCLUSIONS: The sedative properties of the H(1) antihistamines obtained from VAS analysis were very similar to those of H1R occupancy from positron emission tomography (PET) studies and PIR from meta-analysis. Our results indicate that large-scale surveillance using VAS might be useful to evaluate the profiles of H(1) antihistamines."},"publication_date":"2008-07-01","publication_name":{"en":"Allergology International","ja":"Allergology International"},"volume":"Vol.57","number":"No.3","starting_page":"257","ending_page":"263","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2332/allergolint.O-07-525"],"issn":["1323-8930"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18544899","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212510","label":"url"}],"paper_title":{"en":"Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect.","ja":"Suppression of histamine signaling by probiotic Lac-B: a possible mechanism of its anti-allergic effect."},"authors":{"en":[{"name":"Dev Shrabanti"},{"name":"Mizuguchi Hiroyuki"},{"name":"Das Asish K"},{"name":"Matsushita Chiyo"},{"name":"Maeyama Kazutaka"},{"name":"Umehara Hayato"},{"name":"Ohtoshi Takayuki"},{"name":"Kojima Jun"},{"name":"Nishida Kiyotaka"},{"name":"Takahashi Kunihiko"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Dev Shrabanti"},{"name":"水口 博之"},{"name":"Das Asish K"},{"name":"Matsushita Chiyo"},{"name":"Maeyama Kazutaka"},{"name":"Umehara Hayato"},{"name":"Ohtoshi Takayuki"},{"name":"Kojima Jun"},{"name":"Nishida Kiyotaka"},{"name":"Takahashi Kunihiko"},{"name":"福井 裕行"}]},"description":{"en":"It has been shown that probiotic bacteria are effective for the treatment of allergic diseases. As histamine plays a central role in allergic diseases, it is possible that probiotic bacteria affect the allergy-related histamine signaling. Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. In the nasal allergy model rats made by sensitization and provocation with toluene 2,4-diisocyanate (TDI) for 3 weeks, TDI provocation caused acute allergy-like behaviors along with significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNA expression, increased HDC activity, histamine content, and [(3)H]mepyramine binding activity in nasal mucosa. Prolonged treatment with Lac-B (40 mg/rat, p.o.) significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling. Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. Suppression of histamine signaling may be a novel target of probiotics in preventing allergic diseases.","ja":"It has been shown that probiotic bacteria are effective for the treatment of allergic diseases. As histamine plays a central role in allergic diseases, it is possible that probiotic bacteria affect the allergy-related histamine signaling. Here, we investigated the effect of Lac-B, a mixture of freeze-dried Bifidobacterium infantis and Bifidobacterium longum, on the allergy-related histamine signaling. In the nasal allergy model rats made by sensitization and provocation with toluene 2,4-diisocyanate (TDI) for 3 weeks, TDI provocation caused acute allergy-like behaviors along with significant up-regulation of histamine H(1) receptor (H1R) and histidine decarboxylase (HDC) mRNA expression, increased HDC activity, histamine content, and [(3)H]mepyramine binding activity in nasal mucosa. Prolonged treatment with Lac-B (40 mg/rat, p.o.) significantly suppressed both the allergy-like behaviors and all of the above mentioned factors involved in histamine signaling. Our findings indicate that oral administration of Lac-B showed significant anti-allergic effect through suppression of both H1R and HDC gene expression followed by decrease in H1R, HDC protein level, and histamine content. Suppression of histamine signaling may be a novel target of probiotics in preventing allergic diseases."},"publication_date":"2008-06-05","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.107","number":"No.2","starting_page":"159","ending_page":"166","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.08028FP"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=187864","label":"url"}],"paper_title":{"en":"鼻過敏症モデルおけるヒスタミンH1受容体発現上昇機構とその制御について","ja":"鼻過敏症モデルおけるヒスタミンH1受容体発現上昇機構とその制御について"},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"黒田 若奈"},{"name":"DasAsish K"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"黒田 若奈"},{"name":"DasAsish K"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"publication_date":"2008-06","publication_name":{"en":"頭頚部自律神経","ja":"頭頚部自律神経"},"volume":"Vol.22","starting_page":"24","ending_page":"26","referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18597008","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=173448","label":"url"}],"paper_title":{"en":"Disease dependent incidence of sedation of H1 antihistamines found by large-scale surveillance using visual analogue scale (VAS).","ja":"Disease dependent incidence of sedation of H1 antihistamines found by large-scale surveillance using visual analogue scale (VAS)."},"authors":{"en":[{"name":"Izumi, Norimasa"},{"name":"Mizuguchi Hiroyuki"},{"name":"Umehara, Hayato"},{"name":"Ogino, Satoshi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Izumi, Norimasa"},{"name":"水口 博之"},{"name":"Umehara, Hayato"},{"name":"Ogino, Satoshi"},{"name":"福井 裕行"}]},"description":{"en":"Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.","ja":"Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL."},"publication_date":"2008-04","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.30","number":"No.3","starting_page":"225","ending_page":"230","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2008.30.3.1186087"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18498711","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212515","label":"url"}],"paper_title":{"en":"Down-regulation of histamine H1 receptors by beta2-adrenoceptor-mediated inhibition of H1 receptor gene transcription.","ja":"Down-regulation of histamine H1 receptors by beta2-adrenoceptor-mediated inhibition of H1 receptor gene transcription."},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Umehara Hayato"},{"name":"Fujimoto Katsumi"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"河上 希"},{"name":"梅原 隼人"},{"name":"Fujimoto Katsumi"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H1 receptor (H1R) levels vary under various pathological conditions, and these changes may be responsible for some pathogenesis such as in allergic rhinitis. Several stimulants, including histamine, muscarinic agonists and platelet-activating factor, have now been shown to regulate H1R levels and may have roles in regulating the H1R level in physiological and pathological conditions. Results for beta2-adrenoceptor (beta2AR) stimulation are conflicting, however.beta2AR up-regulated H1R in bovine tracheal smooth muscle, but down-regulated human H1R expressed in Chinese hamster ovary (CHO) cells. It is possible that this discrepancy comes from the differences in the preparations used for each study: the former cell expressed bovine H1R and the latter cell expressed human H1R. Moreover, CHO cells have been shown to be inadequate for studying the effects on H1R gene expression, because the cells express non-endogenous stably transfected H1R under the control of the SV40 promoter. Therefore, in this study, we have investigated the role of beta2AR stimulation in H1R gene regulation using human U373 astrocytoma cells that express endogenous H1R and transfected beta2AR. Stimulation of beta2AR significantly reduced H1R promoter activity and H1R mRNA levels. H1R mRNA stability was slightly reduced by beta2AR stimulation, although this was not significant. The decrease of H1R mRNA by beta2AR stimulation was blocked by the protein kinase A (PKA) inhibitor KT5720, suggesting the involvement of PKA. These results indicate that the beta2AR is involved in the down-regulation of human H1R by inhibiting H1R gene transcription through a PKA-dependent process.","ja":"Histamine H1 receptor (H1R) levels vary under various pathological conditions, and these changes may be responsible for some pathogenesis such as in allergic rhinitis. Several stimulants, including histamine, muscarinic agonists and platelet-activating factor, have now been shown to regulate H1R levels and may have roles in regulating the H1R level in physiological and pathological conditions. Results for beta2-adrenoceptor (beta2AR) stimulation are conflicting, however.beta2AR up-regulated H1R in bovine tracheal smooth muscle, but down-regulated human H1R expressed in Chinese hamster ovary (CHO) cells. It is possible that this discrepancy comes from the differences in the preparations used for each study: the former cell expressed bovine H1R and the latter cell expressed human H1R. Moreover, CHO cells have been shown to be inadequate for studying the effects on H1R gene expression, because the cells express non-endogenous stably transfected H1R under the control of the SV40 promoter. Therefore, in this study, we have investigated the role of beta2AR stimulation in H1R gene regulation using human U373 astrocytoma cells that express endogenous H1R and transfected beta2AR. Stimulation of beta2AR significantly reduced H1R promoter activity and H1R mRNA levels. H1R mRNA stability was slightly reduced by beta2AR stimulation, although this was not significant. The decrease of H1R mRNA by beta2AR stimulation was blocked by the protein kinase A (PKA) inhibitor KT5720, suggesting the involvement of PKA. These results indicate that the beta2AR is involved in the down-regulation of human H1R by inhibiting H1R gene transcription through a PKA-dependent process."},"publication_date":"2008","publication_name":{"en":"The Journal of Pharmacy and Pharmacology","ja":"The Journal of Pharmacy and Pharmacology"},"volume":"Vol.60","number":"No.6","starting_page":"747","ending_page":"752","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1211/jpp.60.6.0010"],"issn":["0022-3573"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17409634","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212518","label":"url"}],"paper_title":{"en":"Stimulation of histamine H1 receptor up-regulates histamine H1 receptor itself through activation of receptor gene transcription.","ja":"Stimulation of histamine H1 receptor up-regulates histamine H1 receptor itself through activation of receptor gene transcription."},"authors":{"en":[{"name":"Das Asish K"},{"name":"Yoshimura Sachiho"},{"name":"Mishima Ryoko"},{"name":"Fujimoto Katsumi"},{"name":"Mizuguchi Hiroyuki"},{"name":"Dev Shrabanti"},{"name":"Wakayama Yousuke"},{"name":"Kitamura Yoshiaki"},{"name":"Horio Shuhei"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Das Asish K"},{"name":"Yoshimura Sachiho"},{"name":"Mishima Ryoko"},{"name":"Fujimoto Katsumi"},{"name":"水口 博之"},{"name":"Dev Shrabanti"},{"name":"Wakayama Yousuke"},{"name":"北村 嘉章"},{"name":"堀尾 修平"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"Histamine is a major mediator in allergy acting mainly through the histamine H(1) receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H(2) receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced up-regulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.","ja":"Histamine is a major mediator in allergy acting mainly through the histamine H(1) receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H(2) receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced up-regulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases."},"publication_date":"2007-03","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.103","number":"No.4","starting_page":"374","ending_page":"382","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FP0061411"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17637176","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212517","label":"url"}],"paper_title":{"en":"Heterologous up-regulation of the histamine H1 receptor by M3 muscarinic receptor-mediated activation of H1-receptor gene transcription.","ja":"Heterologous up-regulation of the histamine H1 receptor by M3 muscarinic receptor-mediated activation of H1-receptor gene transcription."},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Das Asish Kumar"},{"name":"Fujimoto Katsumi"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Das Asish Kumar"},{"name":"Fujimoto Katsumi"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H(1) receptor (H1R) level varies under various pathological conditions, and these changes may be responsible for some pathogenesis, such as allergic rhinitis. Previously, we showed that H1R was heterologously down-regulated (through degradation of H1R) by prolonged stimulation with muscarinic M(3) receptor (M3R) in Chinese hamster ovary (CHO) cells stably expressing H1R and M3R. However, this cell was inadequate for studying the effects on H1R gene regulation, because the cell expresses H1R, which is under the control of the SV40 promoter. Therefore, in this study, we have investigated the possible role of M3R stimulation in the H1R gene transcription and H1R mRNA stability by using U373 astrocytoma cells that express endogenous H1R and transfected M3R. Stimulation of M3R significantly increased H1R promoter activity and H1R mRNA level without alteration in H1R mRNA stability. The H1R level was also up-regulated by M3R activation (150% of control by treatment with carbachol for 24 h). These M3R-mediated events were almost completely blocked by the protein kinase C (PKC) inhibitor, Ro 31-8220, suggesting the involvement of PKC. These results indicated that M3R was involved in the up-regulation of H1R by activating H1R gene transcription through a PKC-dependent process.","ja":"Histamine H(1) receptor (H1R) level varies under various pathological conditions, and these changes may be responsible for some pathogenesis, such as allergic rhinitis. Previously, we showed that H1R was heterologously down-regulated (through degradation of H1R) by prolonged stimulation with muscarinic M(3) receptor (M3R) in Chinese hamster ovary (CHO) cells stably expressing H1R and M3R. However, this cell was inadequate for studying the effects on H1R gene regulation, because the cell expresses H1R, which is under the control of the SV40 promoter. Therefore, in this study, we have investigated the possible role of M3R stimulation in the H1R gene transcription and H1R mRNA stability by using U373 astrocytoma cells that express endogenous H1R and transfected M3R. Stimulation of M3R significantly increased H1R promoter activity and H1R mRNA level without alteration in H1R mRNA stability. The H1R level was also up-regulated by M3R activation (150% of control by treatment with carbachol for 24 h). These M3R-mediated events were almost completely blocked by the protein kinase C (PKC) inhibitor, Ro 31-8220, suggesting the involvement of PKC. These results indicated that M3R was involved in the up-regulation of H1R by activating H1R gene transcription through a PKC-dependent process."},"publication_date":"2007","publication_name":{"en":"The Journal of Pharmacy and Pharmacology","ja":"The Journal of Pharmacy and Pharmacology"},"volume":"Vol.59","number":"No.6","starting_page":"843","ending_page":"848","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1211/jpp.59.6.0010"],"issn":["0022-3573"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17099293","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-33751251718&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=164465","label":"url"}],"paper_title":{"en":"Localized expression of histamine H1 receptors in syncytiotrophoblast cells of human placenta.","ja":"Localized expression of histamine H1 receptors in syncytiotrophoblast cells of human placenta."},"authors":{"en":[{"name":"Matsuyama Kazuto"},{"name":"Ichikawa Tatsuya"},{"name":"Nitta Yuichi"},{"name":"Ikoma Yoshio"},{"name":"Ishimura Kazutaka"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"松山 和渡"},{"name":"市川 竜也"},{"name":"新田 雄一"},{"name":"生駒 良雄"},{"name":"Ishimura Kazutaka"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"The previous Northern blot analysis and in situ hybridization studies showed that histamine H1-receptor (H1R) mRNA is expressed in human placenta and suggested that H(1)R plays some roles in the function of placenta in pregnancy. To investigate further, it is essential to show the precise location of H1R in the placenta. In the present study, we investigated H1R expression in human placenta by radioligand binding assay and immunohistochemical study using an antibody against human H1R. Placentas were obtained from normal uncomplicated deliveries. Membranes prepared from the tissue exhibited saturable [3H]mepyramine binding (K(d) = 4.0 +/- 0.6 nM and B(max) = 91.4 +/- 4.9 fmol/mg of protein). Stereoisomers of chlorpheniramine inhibited [(3)H]mepyramine binding; d-chlorpheniramine inhibited more potently than l-chlorpheniramine, K(i) values being 1.1 +/- 0.4 and 270 +/- 170 nM, respectively. The placenta tissues were positively immunostained with anti-H1R antibody only in the region of the syncytiotrophoblast of chorionic villus. The tissues were double stained with anti-H1R antibody and an antibody against human chorionic gonadotoropin (hCG) that is solely expressed in placental syncytiotrophoblast cells. The results showed that H1R and hCG were expressed on the same cells, that is, syncytiotrophoblast cells. These results indicate that H1Rs are specifically expressed in syncytiotrophoblast cells of human placenta organ.","ja":"The previous Northern blot analysis and in situ hybridization studies showed that histamine H1-receptor (H1R) mRNA is expressed in human placenta and suggested that H(1)R plays some roles in the function of placenta in pregnancy. To investigate further, it is essential to show the precise location of H1R in the placenta. In the present study, we investigated H1R expression in human placenta by radioligand binding assay and immunohistochemical study using an antibody against human H1R. Placentas were obtained from normal uncomplicated deliveries. Membranes prepared from the tissue exhibited saturable [3H]mepyramine binding (K(d) = 4.0 +/- 0.6 nM and B(max) = 91.4 +/- 4.9 fmol/mg of protein). Stereoisomers of chlorpheniramine inhibited [(3)H]mepyramine binding; d-chlorpheniramine inhibited more potently than l-chlorpheniramine, K(i) values being 1.1 +/- 0.4 and 270 +/- 170 nM, respectively. The placenta tissues were positively immunostained with anti-H1R antibody only in the region of the syncytiotrophoblast of chorionic villus. The tissues were double stained with anti-H1R antibody and an antibody against human chorionic gonadotoropin (hCG) that is solely expressed in placental syncytiotrophoblast cells. The results showed that H1R and hCG were expressed on the same cells, that is, syncytiotrophoblast cells. These results indicate that H1Rs are specifically expressed in syncytiotrophoblast cells of human placenta organ."},"publication_date":"2006-10","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.102","number":"No.3","starting_page":"331","ending_page":"337","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FP0060862"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17075268","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-33748930011&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212521","label":"url"}],"paper_title":{"en":"Dexamethasone suppresses histamine synthesis by repressing both transcription and activity of HDC in allergic rats.","ja":"Dexamethasone suppresses histamine synthesis by repressing both transcription and activity of HDC in allergic rats."},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Das Asish K"},{"name":"Shimamura Takayuki"},{"name":"Maeyama Kazutaka"},{"name":"Dev Shrabanti"},{"name":"Wakayama Yousuke"},{"name":"Kalubi Bukasa"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"北村 嘉章"},{"name":"Das Asish K"},{"name":"島村 隆之"},{"name":"Maeyama Kazutaka"},{"name":"Dev Shrabanti"},{"name":"Wakayama Yousuke"},{"name":"カルビ ブカサ"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"description":{"en":"BACKGROUND: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectives of the present study were to examine the changes of histamine content, HDC activity and HDC mRNA expression in the nasal mucosa of allergy model rats sensitized by the exposure to toluene diisocyanate (TDI) and to investigate the effect of dexamethasone on the above mentioned allergic parameters. METHODS: Rats were sensitized and provocated by TDI and the nasal allergy-like behaviors were scored during a 10 minute period after provocation. Histamine content and HDC activity in the nasal mucosa were determined using fluorometric high performance liquid chromatography. The expression of HDC mRNA in nasal mucosa was determined using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In TDI-sensitized rats, nasal allergy-like behaviors such as sneezing and watery rhinorrhea were induced. Histamine content, HDC activity and HDC mRNA expression in nasal mucosa were also significantly increased after TDI provocation. Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats. CONCLUSIONS: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Repression of HDC gene expression and HDC activity by dexamethasone may underlie its therapeutic effect in the treatment of allergy.","ja":"BACKGROUND: Histamine synthesized by histidine decarboxylase (HDC) from L-histidine is a major chemical mediator in the development of nasal allergy which is characterized by nasal hypersensitivity. However the regulatory mechanism of histamine synthesis by HDC remains to be elucidated. The objectives of the present study were to examine the changes of histamine content, HDC activity and HDC mRNA expression in the nasal mucosa of allergy model rats sensitized by the exposure to toluene diisocyanate (TDI) and to investigate the effect of dexamethasone on the above mentioned allergic parameters. METHODS: Rats were sensitized and provocated by TDI and the nasal allergy-like behaviors were scored during a 10 minute period after provocation. Histamine content and HDC activity in the nasal mucosa were determined using fluorometric high performance liquid chromatography. The expression of HDC mRNA in nasal mucosa was determined using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In TDI-sensitized rats, nasal allergy-like behaviors such as sneezing and watery rhinorrhea were induced. Histamine content, HDC activity and HDC mRNA expression in nasal mucosa were also significantly increased after TDI provocation. Pretreatment with dexamethasone significantly suppressed nasal allergy-like behaviors, up-regulation of histamine content, HDC activity and HDC mRNA induced by TDI in TDI-sensitized rats. CONCLUSIONS: These findings indicate that increased synthesis of histamine through up-regulation of HDC gene expression and HDC activity in nasal mucosa plays an important role in the development of nasal hypersensitivity. Repression of HDC gene expression and HDC activity by dexamethasone may underlie its therapeutic effect in the treatment of allergy."},"publication_date":"2006-06","publication_name":{"en":"Allergology International","ja":"Allergology International"},"volume":"Vol.55","number":"No.3","starting_page":"279","ending_page":"286","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2332/allergolint.55.279"],"issn":["1323-8930"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16648669","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212522","label":"url"}],"paper_title":{"en":"Recent advances in molecular pharmacology of the histamine systems: regulation of histamine H1 receptor signaling by changing its expression level.","ja":"Recent advances in molecular pharmacology of the histamine systems: regulation of histamine H1 receptor signaling by changing its expression level."},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Das Asish Kumar"},{"name":"Fujimoto Katsumi"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"Das Asish Kumar"},{"name":"Fujimoto Katsumi"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"Histamine H1 receptor (H1R) signaling is regulated by changing its expression level. Two mechanisms are involved in this regulation. One is down-regulation through receptor desensitization. Receptor phosphorylation seemed crucial because stimulation of the mutant H1R lacking five putative phosphorylation sites did not show down-regulation. The phosphorylation level of the mutant receptor was much smaller than that of the wild type ones by several protein kinases. The other is up-regulation through activation of receptor gene expression. Protein kinase C (PKC) signaling was suggested to be involved in this up-regulation. Regulation of H1R expression level was mediated not only through H1R but also autonomic nerve receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down-regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed not to be mediated by PKC activation, although PKC activation induced H1R phosphorylation. Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of beta2-adrenergic receptors induced H1R down-regulation through several mechanisms. One of them is enhanced receptor degradation after desensitization and another is suppression of receptor synthesis that includes the suppression of receptor gene expression and enhanced degradation of the receptor mRNA. Protein kinase A was suggested to be involved in enhanced degradation and the activation of the receptor gene expression. Elevation of both H1R expression and its mRNA was observed in nasal mucosa of nasal hypersensitivity allergy model rat after toluene diisocyanate provocation. These results suggest that activation of H1R gene expression plays an important patho-physiological role in allergy. Elevation of the mRNA was partially but significantly suppressed by antihistamines.","ja":"Histamine H1 receptor (H1R) signaling is regulated by changing its expression level. Two mechanisms are involved in this regulation. One is down-regulation through receptor desensitization. Receptor phosphorylation seemed crucial because stimulation of the mutant H1R lacking five putative phosphorylation sites did not show down-regulation. The phosphorylation level of the mutant receptor was much smaller than that of the wild type ones by several protein kinases. The other is up-regulation through activation of receptor gene expression. Protein kinase C (PKC) signaling was suggested to be involved in this up-regulation. Regulation of H1R expression level was mediated not only through H1R but also autonomic nerve receptors. Stimulation of M3 muscarinic receptors (M3R) induced both down-regulation and up-regulation of H1R. Down-regulation of M3R-mediated H1R seemed not to be mediated by PKC activation, although PKC activation induced H1R phosphorylation. Elevation of H1R expression was induced by the stimulation of M3Rs. PKC was suggested to be involved in this up-regulation. Stimulation of beta2-adrenergic receptors induced H1R down-regulation through several mechanisms. One of them is enhanced receptor degradation after desensitization and another is suppression of receptor synthesis that includes the suppression of receptor gene expression and enhanced degradation of the receptor mRNA. Protein kinase A was suggested to be involved in enhanced degradation and the activation of the receptor gene expression. Elevation of both H1R expression and its mRNA was observed in nasal mucosa of nasal hypersensitivity allergy model rat after toluene diisocyanate provocation. These results suggest that activation of H1R gene expression plays an important patho-physiological role in allergy. Elevation of the mRNA was partially but significantly suppressed by antihistamines."},"publication_date":"2006-04-28","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.101","number":"No.1","starting_page":"3","ending_page":"6","languages":["eng"],"referee":true,"invited":true,"identifiers":{"doi":["10.1254/jphs.FMJ06001X2"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.jstage.jst.go.jp/article/jphs/96/4/96_474/_article/-char/ja/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15599091","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282680151979904/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132242","label":"url"}],"paper_title":{"en":"Homologous and Heterologous Phosphorylations of Human Histamine H1 Receptor in Intact Cells","ja":"Homologous and Heterologous Phosphorylations of Human Histamine H1 Receptor in Intact Cells"},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"河上 希"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"Homologous and heterologous phosphorylations of histamine H1 receptor (H1R) in intact cells were investigated using Chinese hamster ovary cells stably co-expressing c-myc-tagged human histamine H1 and muscarinic M3 receptors. Increase in histamine-induced homologous phosphorylation of H1R was induced in a dose- and time-dependent manner. Maximum phosphorylation of H1R by 8-fold over the basal level was induced 1 min after the stimulation, and the increased phosphorylation level was maintained over 40 min. M3 receptor-mediated heterologous phosphorylation of H1R reached maximum by 2-fold over the basal level at 5 min after the stimulation and then rapidly returned to the basal level by 40 min after the stimulation. Histamine-induced phosphorylation of H1R was partially inhibited by three protein kinase inhibitors including Ro-31-8220 for protein kinase C (PKC), KN-93 for calcium/calmodulin-dependent kinase II (CaMKII), and KT5823 for protein kinase G (PKG), while, M3-receptor-mediated phosphorylation of H1R was completely inhibited by Ro 31-8220. Protein kinase activators including phorbol 12-myristate 13-acetate (PMA), 8-bromo-cyclic GMP (8-Br-cGMP), and 8-bromo-cyclic AMP (8-Br-cAMP) induced increases in H1R phosphorylation. Increased phosphorylation of H1R, by 5-fold over the basal level, induced with a combination of PMA, 8-Br-cGMP, and 8-Br-cAMP was still lower than that with histamine. It was suggested that H1R-mediated H1R phosphorylation involves the activation of PKC, CaMKII, PKG, and other unidentified kinases including G-protein coupled receptor kinases (GRKs) and that PKC is solely involved in M3 receptor-mediated H1R phosphorylation.","ja":"Homologous and heterologous phosphorylations of histamine H1 receptor (H1R) in intact cells were investigated using Chinese hamster ovary cells stably co-expressing c-myc-tagged human histamine H1 and muscarinic M3 receptors. Increase in histamine-induced homologous phosphorylation of H1R was induced in a dose- and time-dependent manner. Maximum phosphorylation of H1R by 8-fold over the basal level was induced 1 min after the stimulation, and the increased phosphorylation level was maintained over 40 min. M3 receptor-mediated heterologous phosphorylation of H1R reached maximum by 2-fold over the basal level at 5 min after the stimulation and then rapidly returned to the basal level by 40 min after the stimulation. Histamine-induced phosphorylation of H1R was partially inhibited by three protein kinase inhibitors including Ro-31-8220 for protein kinase C (PKC), KN-93 for calcium/calmodulin-dependent kinase II (CaMKII), and KT5823 for protein kinase G (PKG), while, M3-receptor-mediated phosphorylation of H1R was completely inhibited by Ro 31-8220. Protein kinase activators including phorbol 12-myristate 13-acetate (PMA), 8-bromo-cyclic GMP (8-Br-cGMP), and 8-bromo-cyclic AMP (8-Br-cAMP) induced increases in H1R phosphorylation. Increased phosphorylation of H1R, by 5-fold over the basal level, induced with a combination of PMA, 8-Br-cGMP, and 8-Br-cAMP was still lower than that with histamine. It was suggested that H1R-mediated H1R phosphorylation involves the activation of PKC, CaMKII, PKG, and other unidentified kinases including G-protein coupled receptor kinases (GRKs) and that PKC is solely involved in M3 receptor-mediated H1R phosphorylation."},"publication_date":"2004-12-15","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.96","number":"No.4","starting_page":"474","ending_page":"482","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FPJ04031X"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15286428","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282680151945344/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212527","label":"url"}],"paper_title":{"en":"Histamine H1 receptor down-regulation mediated by M3 muscarinic acetylcholine receptor subtype.","ja":"Histamine H1 receptor down-regulation mediated by M3 muscarinic acetylcholine receptor subtype."},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Wakayama Yousuke"},{"name":"Izumi Norimasa"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"河上 希"},{"name":"Wakayama Yousuke"},{"name":"Izumi Norimasa"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"Heterologous down-regulation of histamine H(1) receptor (H1R) mediated by muscarinic acetylcholine receptor subtype was investigated using five kinds of Chinese hamster ovary (CHO) cells stably co-expressing the human H1R and one of the five (M(1) - M(5)) muscarinic acetylcholine receptors, CHO-H1/M1, CHO-H1/M2, CHO-H1/M3, CHO-H1/M4, and CHO-H1/M5 cells. Among the CHO-H1/M1, CHO-H1/M3, and CHO-H1/M5 cells, carbachol treatment of the CHO-H1/M3 cells time-dependently led to remarkable down-regulation of the H1R to 60% of the control level. In contrast, stimulation of CHO-H1/M1 cells by carbachol induced negligible effect on the down-regulation. Stimulation of CHO-H1/M5 cells by carbachol induced significant but only small H1R down-regulation. M(2) and M(4) muscarinic receptors showed negligible effect on the down-regulation. H1R-mediated accumulation of inositol phosphates in CHO-H1/M3 cells with long-term expose to carbachol was decreased to 60% compared with non-treated cells. Heterologous phosphorylation of H1R was induced by the stimulation of each muscarinic receptor. H1R was phosphorylated by about twofold from the basal level through five subtypes of muscarinic receptor. The M(3) muscarinic receptor-mediated phosphorylation of H1R was reversed by the inhibition of protein kinase C. In the present study we demonstrated that the M(3) muscarinic acetylcholine receptor mediated remarkable down-regulation of the H1R with decreased receptor signaling.","ja":"Heterologous down-regulation of histamine H(1) receptor (H1R) mediated by muscarinic acetylcholine receptor subtype was investigated using five kinds of Chinese hamster ovary (CHO) cells stably co-expressing the human H1R and one of the five (M(1) - M(5)) muscarinic acetylcholine receptors, CHO-H1/M1, CHO-H1/M2, CHO-H1/M3, CHO-H1/M4, and CHO-H1/M5 cells. Among the CHO-H1/M1, CHO-H1/M3, and CHO-H1/M5 cells, carbachol treatment of the CHO-H1/M3 cells time-dependently led to remarkable down-regulation of the H1R to 60% of the control level. In contrast, stimulation of CHO-H1/M1 cells by carbachol induced negligible effect on the down-regulation. Stimulation of CHO-H1/M5 cells by carbachol induced significant but only small H1R down-regulation. M(2) and M(4) muscarinic receptors showed negligible effect on the down-regulation. H1R-mediated accumulation of inositol phosphates in CHO-H1/M3 cells with long-term expose to carbachol was decreased to 60% compared with non-treated cells. Heterologous phosphorylation of H1R was induced by the stimulation of each muscarinic receptor. H1R was phosphorylated by about twofold from the basal level through five subtypes of muscarinic receptor. The M(3) muscarinic receptor-mediated phosphorylation of H1R was reversed by the inhibition of protein kinase C. In the present study we demonstrated that the M(3) muscarinic acetylcholine receptor mediated remarkable down-regulation of the H1R with decreased receptor signaling."},"publication_date":"2004-07-24","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.95","number":"No.4","starting_page":"426","ending_page":"434","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FPJ04012X"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://jpet.aspetjournals.org/cgi/content/abstract/309/2/786","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14752062","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132241","label":"url"}],"paper_title":{"en":"Histamine H1 and H2 Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans","ja":"Histamine H1 and H2 Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans"},"authors":{"en":[{"name":"Matsuda Naoyuki"},{"name":"Jesmin Subrina"},{"name":"Takahashi Yoshika"},{"name":"Hatta Eiichiro"},{"name":"Kobayashi Masanobu"},{"name":"Matsuyama Kazuto"},{"name":"Kawakami Nozomi"},{"name":"Sakuma Ichiro"},{"name":"Gando Satoshi"},{"name":"Fukui Hiroyuki"},{"name":"Hattori Yuichi"},{"name":"Levi Roberto"}],"ja":[{"name":"Matsuda Naoyuki"},{"name":"Jesmin Subrina"},{"name":"Takahashi Yoshika"},{"name":"Hatta Eiichiro"},{"name":"Kobayashi Masanobu"},{"name":"Matsuyama Kazuto"},{"name":"Kawakami Nozomi"},{"name":"Sakuma Ichiro"},{"name":"Gando Satoshi"},{"name":"福井 裕行"},{"name":"Hattori Yuichi"},{"name":"Levi Roberto"}]},"description":{"en":"Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H(1) and H(2) receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H(1) and H(2) receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H(1) and H(2) receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H(1) and H(2) receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H(1) and H(2) receptors are variably distributed among different mammalian species and different regions of the heart, whereas H(2) receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H(1) and H(2) receptors. The highly abundant expression of H(2) receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.","ja":"Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H(1) and H(2) receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H(1) and H(2) receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H(1) and H(2) receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H(1) and H(2) receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H(1) and H(2) receptors are variably distributed among different mammalian species and different regions of the heart, whereas H(2) receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H(1) and H(2) receptors. The highly abundant expression of H(2) receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions."},"publication_date":"2004-05","publication_name":{"en":"The Journal of Pharmacology and Experimental Therapeutics","ja":"The Journal of Pharmacology and Experimental Therapeutics"},"volume":"Vol.309","number":"No.2","starting_page":"786","ending_page":"795","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1124/jpet.103.063065"],"issn":["0022-3565"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/130000073832/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15107581","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282680153154176/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=87010","label":"url"}],"paper_title":{"en":"Identification of amino acid residues responsible for agonist-induced down-regulation of histamine H1 receptors.","ja":"Identification of amino acid residues responsible for agonist-induced down-regulation of histamine H1 receptors."},"authors":{"en":[{"name":"Horio Shuhei"},{"name":"Ogawa Maki"},{"name":"Kawakami Nozomi"},{"name":"Fujimoto Katsumi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"堀尾 修平"},{"name":"Ogawa Maki"},{"name":"河上 希"},{"name":"Fujimoto Katsumi"},{"name":"福井 裕行"}]},"description":{"en":"The histamine H1 receptor (H1R) level is dynamically regulated in vivo under various physiological and pathological conditions. The H1R regulation may consist of various processes, and this study focused on the process of receptor trafficking, that is, receptor internalization to endosomes and the following receptor degradation. First, we identified five possible phosphorylation residues of human H1R, Thr140, Thr142, Ser396, Ser398, and Thr478, based on in vitro phosphorylation studies. Then to determine the role of these residues, we constructed a mutant H1R in which all of these five residues were substituted with alanine. Both wild-type and the mutant receptors expressed in Chinese hamster ovary (CHO) cells had similar values of Kd for [3H]mepyramine binding and Ki for histamine, and these cells showed similar levels of histamine-stimulated inositol phosphate formation. Both types of H1Rs were internalized essentially in the same way upon stimulation with histamine (100 μM) for 30 min. However, down-regulation of the mutant H1R was completely impaired, whereas that of wild-type H1R occurred by approximately 60% by the treatment with 100 μM histamine for 24 h. These results suggest that these residues are responsible for receptor down-regulation but not for receptor internalization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes.","ja":"The histamine H1 receptor (H1R) level is dynamically regulated in vivo under various physiological and pathological conditions. The H1R regulation may consist of various processes, and this study focused on the process of receptor trafficking, that is, receptor internalization to endosomes and the following receptor degradation. First, we identified five possible phosphorylation residues of human H1R, Thr140, Thr142, Ser396, Ser398, and Thr478, based on in vitro phosphorylation studies. Then to determine the role of these residues, we constructed a mutant H1R in which all of these five residues were substituted with alanine. Both wild-type and the mutant receptors expressed in Chinese hamster ovary (CHO) cells had similar values of Kd for [3H]mepyramine binding and Ki for histamine, and these cells showed similar levels of histamine-stimulated inositol phosphate formation. Both types of H1Rs were internalized essentially in the same way upon stimulation with histamine (100 μM) for 30 min. However, down-regulation of the mutant H1R was completely impaired, whereas that of wild-type H1R occurred by approximately 60% by the treatment with 100 μM histamine for 24 h. These results suggest that these residues are responsible for receptor down-regulation but not for receptor internalization. Possibly, phosphorylation of the residues is required for receptor transport from endosomes to lysosomes."},"publication_date":"2004-04-01","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.94","number":"No.4","starting_page":"410","ending_page":"419","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.94.410"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15107586","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-2342483132&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88563","label":"url"}],"paper_title":{"en":"Beta2-adrenergic receptor-mediated histamine H1 receptor down-regulation: another possible advantage of b2 agonists in asthmatic therapy.","ja":"Beta2-adrenergic receptor-mediated histamine H1 receptor down-regulation: another possible advantage of b2 agonists in asthmatic therapy."},"authors":{"en":[{"name":"Kawakami Nozomi"},{"name":"Miyoshi Katsuhiro"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"河上 希"},{"name":"Miyoshi Katsuhiro"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"To clarify heterologous regulation of a receptor is important in considering medication. Histamine constricts the airway smooth muscle through the action to the H(1) receptor (H1R), which contributes to asthma. beta(2)-Adrenergic receptor (beta2R) agonists are widely used in asthmatic therapy for their bronchodilating effects. In this study, we investigated the effect of beta2R activation on the H1R function using Chinese hamster ovary cells stably co-expressing human histamine H1R and beta2R (CHO-H1/beta2 cell). The stimulation of beta2R resulted in the decrease of H1R in the membrane. Heterologous H1R down-regulation was significantly reversed in the presence of the cyclic AMP-dependent protein kinase (PKA) inhibitor KT5720. Since phosphorylation of G protein-coupled receptor (GPCR) by second messenger-dependent kinases, is proposed to be a key step initiating heterologous receptor desensitization, we examined whether heterologous H1R down-regulation was accompanied by H1R phosphorylation. H1R was phosphorylated by beta2R stimulation; however, a PKA inhibitor did not inhibit heterologous H1R phosphorylation. Our results suggest that H1R was heterologously regulated by beta2R. Not only a direct action of beta2R agonist to beta2R causing bronchodilation but also indirect action that reduces the number of H1R responsible for bronchoconstriction might contribute to a decrease in the bronchial resistance, which proposes another possible advantage of beta2R agonists for asthmatic medication.","ja":"To clarify heterologous regulation of a receptor is important in considering medication. Histamine constricts the airway smooth muscle through the action to the H(1) receptor (H1R), which contributes to asthma. beta(2)-Adrenergic receptor (beta2R) agonists are widely used in asthmatic therapy for their bronchodilating effects. In this study, we investigated the effect of beta2R activation on the H1R function using Chinese hamster ovary cells stably co-expressing human histamine H1R and beta2R (CHO-H1/beta2 cell). The stimulation of beta2R resulted in the decrease of H1R in the membrane. Heterologous H1R down-regulation was significantly reversed in the presence of the cyclic AMP-dependent protein kinase (PKA) inhibitor KT5720. Since phosphorylation of G protein-coupled receptor (GPCR) by second messenger-dependent kinases, is proposed to be a key step initiating heterologous receptor desensitization, we examined whether heterologous H1R down-regulation was accompanied by H1R phosphorylation. H1R was phosphorylated by beta2R stimulation; however, a PKA inhibitor did not inhibit heterologous H1R phosphorylation. Our results suggest that H1R was heterologously regulated by beta2R. Not only a direct action of beta2R agonist to beta2R causing bronchodilation but also indirect action that reduces the number of H1R responsible for bronchoconstriction might contribute to a decrease in the bronchial resistance, which proposes another possible advantage of beta2R agonists for asthmatic medication."},"publication_date":"2004-04","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"Vol.94","number":"No.4","starting_page":"449","ending_page":"458","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.94.449"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15328002","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212526","label":"url"}],"paper_title":{"en":"Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H1 receptor downregulation.","ja":"Two threonine residues and two serine residues in the second and third intracellular loops are both involved in histamine H1 receptor downregulation."},"authors":{"en":[{"name":"Horio Shuhei"},{"name":"Kato Toshiyuki"},{"name":"Ogawa Maki"},{"name":"Fujimoto Katsumi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"堀尾 修平"},{"name":"Kato Toshiyuki"},{"name":"Ogawa Maki"},{"name":"Fujimoto Katsumi"},{"name":"福井 裕行"}]},"description":{"en":"Human histamine H1 receptor (H1R) contains five possible phosphorylation residues (Thr140, Thr142, Ser396, Ser398 and Thr478) and the substitution of all these five residues to alanine completely impairs agonist-induced receptor downregulation. In the present study, to determine which residue(s) are responsible for receptor downregulation, we used mutant H1Rs in which single or multiple residues were substituted with alanine. The results suggested that two groups, i.e., residues Thr140 and Thr142, and residues Ser396 and Ser398, independently contributed to H1R downregulation. Thr140 and Ser398 mainly contributed to downregulation, and Thr142 or Ser396 had a slight inhibitory effect on Thr140- or Ser398-mediated process, respectively.","ja":"Human histamine H1 receptor (H1R) contains five possible phosphorylation residues (Thr140, Thr142, Ser396, Ser398 and Thr478) and the substitution of all these five residues to alanine completely impairs agonist-induced receptor downregulation. In the present study, to determine which residue(s) are responsible for receptor downregulation, we used mutant H1Rs in which single or multiple residues were substituted with alanine. The results suggested that two groups, i.e., residues Thr140 and Thr142, and residues Ser396 and Ser398, independently contributed to H1R downregulation. Thr140 and Ser398 mainly contributed to downregulation, and Thr142 or Ser396 had a slight inhibitory effect on Thr140- or Ser398-mediated process, respectively."},"publication_date":"2004","publication_name":{"en":"FEBS Letters","ja":"FEBS Letters"},"volume":"Vol.573","number":"No.1-3","starting_page":"226","ending_page":"230","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.febslet.2004.07.072"],"issn":["0014-5793"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15513549","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212525","label":"url"}],"paper_title":{"en":"Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal mucosa of rats sensitized by exposure to toluene diisocyanate.","ja":"Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal mucosa of rats sensitized by exposure to toluene diisocyanate."},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Miyoshi Ayako"},{"name":"Shimamura Takayuki"},{"name":"Kalubi Bukasa"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Noriaki"}],"ja":[{"name":"北村 嘉章"},{"name":"Miyoshi Ayako"},{"name":"島村 隆之"},{"name":"カルビ ブカサ"},{"name":"福井 裕行"},{"name":"武田 憲昭"}]},"description":{"en":"OBJECTIVE: Histamine is a major chemical mediator in the development of nasal allergy, which is characterized by nasal hypersensitivity. In this study, we used rats sensitized by exposure to toluene diisocyanate (TDI) as an animal model of nasal hypersensitivity and examined changes in expression of histamine H1 receptor (H1R) in the nasal mucosa. The effect of glucocorticoid on upregulation of H1R in nasal mucosa induced by TDI was also examined. MATERIAL AND METHODS: In rats sensitized by exposure to TDI, nasal allergy-like behavior was scored during a 10-min period after TDI provocation. The expression of H1R in the nasal mucosa was determined by means of a real-time quantitative reverse transcriptase polymerase chain reaction and a [3H]mepyramine binding assay. RESULTS: In TDI-sensitized rats, nasal allergy-like behavior, such as sneezing and watery rhinorrhea, was induced after intranasal application of TDI and nasal hypersensitivity to histamine was significantly increased. The level of H1R mRNA expression and the specific binding of [3H]mepyramine in the nasal mucosa were significantly increased after intranasal application of TDI in TDI-sensitized rats. Pretreatment with dexamethasone significantly reduced both nasal allergy-like behavior and the upregulation of H1R induced by TDI in the rats. CONCLUSION: As shown in TDI-sensitized rats, our findings suggest that the upregulation of H1R in the nasal mucosa is one of the mechanisms responsible for nasal hypersensitivity behavior and nasal hypersensitivity to histamine and that the therapeutic effects of dexamethasone are, in part, due to its inhibitory action on the upregulation of H1R.","ja":"OBJECTIVE: Histamine is a major chemical mediator in the development of nasal allergy, which is characterized by nasal hypersensitivity. In this study, we used rats sensitized by exposure to toluene diisocyanate (TDI) as an animal model of nasal hypersensitivity and examined changes in expression of histamine H1 receptor (H1R) in the nasal mucosa. The effect of glucocorticoid on upregulation of H1R in nasal mucosa induced by TDI was also examined. MATERIAL AND METHODS: In rats sensitized by exposure to TDI, nasal allergy-like behavior was scored during a 10-min period after TDI provocation. The expression of H1R in the nasal mucosa was determined by means of a real-time quantitative reverse transcriptase polymerase chain reaction and a [3H]mepyramine binding assay. RESULTS: In TDI-sensitized rats, nasal allergy-like behavior, such as sneezing and watery rhinorrhea, was induced after intranasal application of TDI and nasal hypersensitivity to histamine was significantly increased. The level of H1R mRNA expression and the specific binding of [3H]mepyramine in the nasal mucosa were significantly increased after intranasal application of TDI in TDI-sensitized rats. Pretreatment with dexamethasone significantly reduced both nasal allergy-like behavior and the upregulation of H1R induced by TDI in the rats. CONCLUSION: As shown in TDI-sensitized rats, our findings suggest that the upregulation of H1R in the nasal mucosa is one of the mechanisms responsible for nasal hypersensitivity behavior and nasal hypersensitivity to histamine and that the therapeutic effects of dexamethasone are, in part, due to its inhibitory action on the upregulation of H1R."},"publication_date":"2004","publication_name":{"en":"Acta Oto-Laryngologica","ja":"Acta Oto-Laryngologica"},"volume":"Vol.124","number":"No.9","starting_page":"1053","ending_page":"1058","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/00016480410022525"],"issn":["0001-6489"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14685295","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0347132605&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88572","label":"url"}],"paper_title":{"en":"Direct phosphorylation of histamine H1 receptor by various protein kinases in vitro.","ja":"Direct phosphorylation of histamine H1 receptor by various protein kinases in vitro."},"authors":{"en":[{"name":"Kawakami Nozomi"},{"name":"Miyoshi Katsuhiro"},{"name":"Horio Shuhei"},{"name":"Yoshimura Yoshiyuki"},{"name":"Yamauchi Takashi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Kawakami Nozomi"},{"name":"Miyoshi Katsuhiro"},{"name":"堀尾 修平"},{"name":"吉村 好之"},{"name":"山内 卓"},{"name":"福井 裕行"}]},"description":{"en":"Phosphorylation of G protein-coupled receptors (GPCRs) by various kinases is suggested to be an important step in initiating receptor desensitization. Some reports have indirectly demonstrated the involvement of protein kinase C (PKC)-mediated receptor phosphorylation in the desensitization of the histamine H1 receptor (H1R). In this study, human c-myc-epitope-tagged H1R (hm mcH1R) was expressed in Sf9 cells, and an in vitro approach was taken to obtain direct evidence that H1R could be phosphorylated by various kinases. When hm mcH1R, which had been immunoprecipitated with anti-c-myc antibody from Sf9 cell membranes, was incubated with PKC, cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinase II (CaMKII) or cGMP-dependent protein kinase (PKG), the immunoprecipitated receptor was phosphorylated by these kinases. Membrane-bound hm mcH1R, whose conformation is closer to its physiological state than that of the immunoprecipitated receptor, was also phosphorylated by PKC, PKA, CaMKII and PKG. Phosphorylation of immunoprecipitated and membrane-bound hm mcH1R was inhibited by kinase inhibitors. These data are the first demonstration of the phosphorylation of H1R by four protein kinases, i.e., PKC, PKA, CaMKII and PKG, and provide fundamental information to help us further understand the relationship between H1R phosphorylation and desensitization of this receptor.","ja":"Phosphorylation of G protein-coupled receptors (GPCRs) by various kinases is suggested to be an important step in initiating receptor desensitization. Some reports have indirectly demonstrated the involvement of protein kinase C (PKC)-mediated receptor phosphorylation in the desensitization of the histamine H1 receptor (H1R). In this study, human c-myc-epitope-tagged H1R (hm mcH1R) was expressed in Sf9 cells, and an in vitro approach was taken to obtain direct evidence that H1R could be phosphorylated by various kinases. When hm mcH1R, which had been immunoprecipitated with anti-c-myc antibody from Sf9 cell membranes, was incubated with PKC, cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinase II (CaMKII) or cGMP-dependent protein kinase (PKG), the immunoprecipitated receptor was phosphorylated by these kinases. Membrane-bound hm mcH1R, whose conformation is closer to its physiological state than that of the immunoprecipitated receptor, was also phosphorylated by PKC, PKA, CaMKII and PKG. Phosphorylation of immunoprecipitated and membrane-bound hm mcH1R was inhibited by kinase inhibitors. These data are the first demonstration of the phosphorylation of H1R by four protein kinases, i.e., PKC, PKA, CaMKII and PKG, and provide fundamental information to help us further understand the relationship between H1R phosphorylation and desensitization of this receptor."},"publication_date":"2003-11","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.25","number":"No.9","starting_page":"685","ending_page":"693","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2003.25.9.793335"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12954799","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=212530","label":"url"}],"paper_title":{"en":"Contractions to histamine in pulmonary and mesenteric arteries from endotoxemic rabbits: modulation by vascular expressions of inducible nitric-oxide synthase and histamine H1-receptors.","ja":"Contractions to histamine in pulmonary and mesenteric arteries from endotoxemic rabbits: modulation by vascular expressions of inducible nitric-oxide synthase and histamine H1-receptors."},"authors":{"en":[{"name":"Matsuda Naoyuki"},{"name":"Hattori Yuichi"},{"name":"Zhang Xiao-Hong"},{"name":"Fukui Hiroyuki"},{"name":"Kemmotsu Osamu"},{"name":"Gando Satoshi"}],"ja":[{"name":"Matsuda Naoyuki"},{"name":"Hattori Yuichi"},{"name":"Zhang Xiao-Hong"},{"name":"福井 裕行"},{"name":"Kemmotsu Osamu"},{"name":"Gando Satoshi"}]},"description":{"en":"The inducible isoform of nitric-oxide synthase (iNOS) is highly expressed after induction of endotoxemia and contributes to vascular hypocontractility in endotoxemia. Circulating levels of histamine are elevated in animal models of sepsis and in patients with septic shock. This study assessed whether the vascular effects of histamine play a significant role in the pathophysiology of endotoxemic shock despite the hyporesponsiveness to vasoconstrictors associated with iNOS up-regulation. Rabbits were rendered endotoxemic by lipopolysaccharide (LPS; 100 microg/kg, i.v.). In mesenteric arteries taken from animals at 6 h of LPS administration, the contractile response to histamine was significantly impaired but histamine-evoked contractions in pulmonary arteries were unchanged. Western blot revealed a drastic increase in iNOS expression in mesenteric vessels after LPS, but endotoxin-induced iNOS increase was not so marked in pulmonary vessels. On the other hand, expression of endothelial nitric-oxide synthase was suppressed under LPS challenge in both types of vessels. In the presence of NG-nitro-l-arginine or (S)-ethylisothiourea used for iNOS inhibition, histamine-evoked contractions of endotoxemic pulmonary and mesenteric vessels were significantly enhanced. This was possibly associated with a dramatic increase in H1-receptor expression at the gene and protein levels, as determined by Northern blot and immunoblot analyses. Furthermore, we found that LPS-induced endotoxemia caused prominent increases in production of histamine through induction of histidine decarboxylase in tissues, including blood vessels. From these results, we propose that histamine may contribute to the development of endotoxin-induced pulmonary hypertension.","ja":"The inducible isoform of nitric-oxide synthase (iNOS) is highly expressed after induction of endotoxemia and contributes to vascular hypocontractility in endotoxemia. Circulating levels of histamine are elevated in animal models of sepsis and in patients with septic shock. This study assessed whether the vascular effects of histamine play a significant role in the pathophysiology of endotoxemic shock despite the hyporesponsiveness to vasoconstrictors associated with iNOS up-regulation. Rabbits were rendered endotoxemic by lipopolysaccharide (LPS; 100 microg/kg, i.v.). In mesenteric arteries taken from animals at 6 h of LPS administration, the contractile response to histamine was significantly impaired but histamine-evoked contractions in pulmonary arteries were unchanged. Western blot revealed a drastic increase in iNOS expression in mesenteric vessels after LPS, but endotoxin-induced iNOS increase was not so marked in pulmonary vessels. On the other hand, expression of endothelial nitric-oxide synthase was suppressed under LPS challenge in both types of vessels. In the presence of NG-nitro-l-arginine or (S)-ethylisothiourea used for iNOS inhibition, histamine-evoked contractions of endotoxemic pulmonary and mesenteric vessels were significantly enhanced. This was possibly associated with a dramatic increase in H1-receptor expression at the gene and protein levels, as determined by Northern blot and immunoblot analyses. Furthermore, we found that LPS-induced endotoxemia caused prominent increases in production of histamine through induction of histidine decarboxylase in tissues, including blood vessels. From these results, we propose that histamine may contribute to the development of endotoxin-induced pulmonary hypertension."},"publication_date":"2003-09-03","publication_name":{"en":"The Journal of Pharmacology and Experimental Therapeutics","ja":"The Journal of Pharmacology and Experimental Therapeutics"},"volume":"Vol.307","number":"No.1","starting_page":"175","ending_page":"181","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1124/jpet.103.054163"],"issn":["0022-3565"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12851655","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0037818492&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88576","label":"url"}],"paper_title":{"en":"Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor.","ja":"Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor."},"authors":{"en":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Miyoshi Katsuhiro"},{"name":"Kawakami Nozomi"},{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"The role of various protein kinases in the downregulation of histamine H(1) receptors was studied by using their inhibitors and activators. Human histamine H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine in a dose- and time-dependent manner, and this downregulation continued to increase over a 24-h period. KT5823, an inhibitor of protein kinase G, remarkably but not completely reversed the histamine-induced H(1)R downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP, membrane-permeable analogues of cGMP, did not show any effects on H(1)R downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor of protein kinase C (PKC), did not affect histamine-induced downregulation of H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester. Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP.","ja":"The role of various protein kinases in the downregulation of histamine H(1) receptors was studied by using their inhibitors and activators. Human histamine H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine in a dose- and time-dependent manner, and this downregulation continued to increase over a 24-h period. KT5823, an inhibitor of protein kinase G, remarkably but not completely reversed the histamine-induced H(1)R downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP, membrane-permeable analogues of cGMP, did not show any effects on H(1)R downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor of protein kinase C (PKC), did not affect histamine-induced downregulation of H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester. Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP."},"publication_date":"2003-06","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.25","number":"No.5","starting_page":"343","ending_page":"347","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2003.25.5.769654"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.springerlink.com/(omuva0aikjfmpg45tpwy0m45)/app/home/contribution.asp?referrer=parent&backto=issue,4,6;journal,36,125;linkingpublicationresults,1:101197,1","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12813625","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132226","label":"url"}],"paper_title":{"en":"Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative","ja":"Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative"},"authors":{"en":[{"name":"Fukuda S"},{"name":"Midoro K"},{"name":"Yamasaki M"},{"name":"Gyoten M"},{"name":"Kawano Y"},{"name":"Fukui Hiroyuki"},{"name":"Ashida Y"},{"name":"Nagaya H"}],"ja":[{"name":"Fukuda S"},{"name":"Midoro K"},{"name":"Yamasaki M"},{"name":"Gyoten M"},{"name":"Kawano Y"},{"name":"福井 裕行"},{"name":"Ashida Y"},{"name":"Nagaya H"}]},"description":{"en":"The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.","ja":"The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions."},"publication_date":"2003-04","publication_name":{"en":"Inflammation Research","ja":"Inflammation Research"},"volume":"Vol.52","number":"No.5","starting_page":"206","ending_page":"214","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s000110300073"],"issn":["1023-3830"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12491786","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0036443865&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92621","label":"url"}],"paper_title":{"en":"Expression mechanisms of inducible type nitric oxide synthase gene via interleukin-1 receptor signaling","ja":"Expression mechanisms of inducible type nitric oxide synthase gene via interleukin-1 receptor signaling"},"authors":{"en":[{"name":"Hisayama Tetsuhiro"},{"name":"Shinohara Yasuyuki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"久山 哲廣"},{"name":"篠原 靖幸"},{"name":"福井 裕行"}]},"description":{"en":"The functional study on NF-kB bindings sites in transcription-regulatory region of rat inducible type nitric oxide synthase (iNOS) has been carried out by reporter assay to learn the signaling mechanisms of actions of interleukin-1 (IL-1). By progressive excision of 5'-ends of the insert and introduction of mutagenesis of each NF-kB binding site, it has been shown that 3 kB sites are essential for IL-1-induced signaling pathway in a mutually dependent manner.","ja":"The functional study on NF-kB bindings sites in transcription-regulatory region of rat inducible type nitric oxide synthase (iNOS) has been carried out by reporter assay to learn the signaling mechanisms of actions of interleukin-1 (IL-1). By progressive excision of 5'-ends of the insert and introduction of mutagenesis of each NF-kB binding site, it has been shown that 3 kB sites are essential for IL-1-induced signaling pathway in a mutually dependent manner."},"publication_date":"2002-11","publication_name":{"en":"Folia Pharmacologica Japonica","ja":"日本薬理学雑誌"},"volume":"Vol.120","number":"No.1","starting_page":"76","ending_page":"78","languages":["jpn"],"referee":true,"identifiers":{"issn":["0015-5691"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92610","label":"url"}],"paper_title":{"en":"Involvement of MAP kinase in expression of inducible nitric oxide synthase gene by proinflammatory cytokine interleukin-1.","ja":"Involvement of MAP kinase in expression of inducible nitric oxide synthase gene by proinflammatory cytokine interleukin-1."},"authors":{"en":[{"name":"Hisayama Tetsuhiro"},{"name":"Onki Tatsuhiro"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"久山 哲廣"},{"name":"御木 龍宏"},{"name":"福井 裕行"}]},"publication_date":"2001-10","publication_name":{"en":"Folia Pharmacologica Japonica","ja":"Folia Pharmacologica Japonica"},"volume":"Vol.118","number":"No.1","starting_page":"94","ending_page":"98","referee":true,"identifiers":{"issn":["0015-5691"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://dx.doi.org/10.1016/S0006-8993(01)02287-9","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11368954","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132225","label":"url"}],"paper_title":{"en":"Histamine H1 receptor mRNA is expressed in capsaicin-insensitive sensory neurons with neuropeptide Y-immunoreactivity in guinea pigs","ja":"Histamine H1 receptor mRNA is expressed in capsaicin-insensitive sensory neurons with neuropeptide Y-immunoreactivity in guinea pigs"},"authors":{"en":[{"name":"Kashiba Hitoshi"},{"name":"Fukui Hiroyuki"},{"name":"Senba Emiko"}],"ja":[{"name":"Kashiba Hitoshi"},{"name":"福井 裕行"},{"name":"Senba Emiko"}]},"description":{"en":"Histamine H1 receptor mRNA-expressing sensory neurons in guinea pigs are unmyelinated and are not immunoreactive to substance P and calcitonin gene-related peptide (CGRP) [Mol. Brain Res. 66 (1999) 24], which are implicated in the nociceptive transmission of the primary sensory system. In this study, we examined whether these H1 receptor mRNA-expressing neurons are sensitive to capsaicin by using in situ hybridization histochemistry. Of lumbar dorsal root ganglion (DRG) neurons in control animals, 17% were positive for CGRP. In guinea pigs neonatally treated with capsaicin (50 mg/kg), few CGRP-immunoreactive neurons were seen in the DRGs. However, the percentages of H1 receptor mRNA-expressing neurons (15-20%) and the intensity of the mRNA signals in these neurons were not affected by neonatal capsaicin treatment. We also revealed the presence of both capsaicin-sensitive and insensitive neuropeptide Y (NPY)-immunoreactive neurons in the DRGs. These neurons were exclusively small. H1 receptor mRNA was expressed in NPY-immunoreactive neurons in naive guinea pig DRGs. These results suggest that H1 receptor mRNA is expressed in capsaicin-insensitive DRG neurons with NPY-immunoreactivity in guinea pigs.","ja":"Histamine H1 receptor mRNA-expressing sensory neurons in guinea pigs are unmyelinated and are not immunoreactive to substance P and calcitonin gene-related peptide (CGRP) [Mol. Brain Res. 66 (1999) 24], which are implicated in the nociceptive transmission of the primary sensory system. In this study, we examined whether these H1 receptor mRNA-expressing neurons are sensitive to capsaicin by using in situ hybridization histochemistry. Of lumbar dorsal root ganglion (DRG) neurons in control animals, 17% were positive for CGRP. In guinea pigs neonatally treated with capsaicin (50 mg/kg), few CGRP-immunoreactive neurons were seen in the DRGs. However, the percentages of H1 receptor mRNA-expressing neurons (15-20%) and the intensity of the mRNA signals in these neurons were not affected by neonatal capsaicin treatment. We also revealed the presence of both capsaicin-sensitive and insensitive neuropeptide Y (NPY)-immunoreactive neurons in the DRGs. These neurons were exclusively small. H1 receptor mRNA was expressed in NPY-immunoreactive neurons in naive guinea pig DRGs. These results suggest that H1 receptor mRNA is expressed in capsaicin-insensitive DRG neurons with NPY-immunoreactivity in guinea pigs."},"publication_date":"2001-05-18","publication_name":{"en":"Brain Research","ja":"Brain Research"},"volume":"Vol.901","number":"No.1-2","starting_page":"85","ending_page":"93","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0006-8993(01)02287-9"],"issn":["0006-8993"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.ingentaconnect.com/content/rpsgb/jpp/2001/00000053/00000002/art00015","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11273023","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0035134937&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88586","label":"url"}],"paper_title":{"en":"Inhibition of oxotremorine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.","ja":"Inhibition of oxotremorine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions."},"authors":{"en":[{"name":"Horio Shuhei"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"堀尾 修平"},{"name":"福井 裕行"}]},"description":{"en":"The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10(-7)-10(-5) M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereasthis condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10(-4) M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization.","ja":"The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10(-7)-10(-5) M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereasthis condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10(-4) M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization."},"publication_date":"2001-02-01","publication_name":{"en":"The Journal of Pharmacy and Pharmacology","ja":"The Journal of Pharmacy and Pharmacology"},"volume":"Vol.53","number":"No.2","starting_page":"249","ending_page":"254","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1211/0022357011775271"],"issn":["0022-3573"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=584458","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10939036","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0033947514&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132222","label":"url"}],"paper_title":{"en":"Usefulness and safety of theophylline injection form (Theodrip(R)) for the treatment of acute asthma","ja":"Usefulness and safety of theophylline injection form (Theodrip(R)) for the treatment of acute asthma"},"authors":{"en":[{"name":"Kojima J"},{"name":"Katoh H"},{"name":"Taniguchi T"},{"name":"Kawai H"},{"name":"Fukui Hiroyuki"},{"name":"Ohnishi A"},{"name":"Onodera K"}],"ja":[{"name":"Kojima J"},{"name":"Katoh H"},{"name":"Taniguchi T"},{"name":"Kawai H"},{"name":"福井 裕行"},{"name":"Ohnishi A"},{"name":"Onodera K"}]},"description":{"en":"The effects of the speed of intravenous infusion on the pharmacokinetics of theophylline were studied in 9 healthy volunteers (Ex I). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip, Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and II, Cmax was 10.8 +/- 1.1 and 10.8 +/- 0.8 micrograms/ml, respectively. These Cmaxs were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The 90% confidence limits of the differences of mean values were within 80-120% and were 92.8-100.1% for Cmax, 99.7-105.3% for t1/2 and 100.2-104.4% for AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip (theophylline at 4.8 mg/kg) were bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II, no subjects had adverse effects and in Ex I no influence on ECG was seen. In addition, the convenience of Theodrip was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip were significantly shorter than those of aminophylline ampules. On the other hand, the adverse reactions to aminophylline resulting from hypersensitivity reactions to its ethylenediamine component have been reported. Theodrip consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore, Theodrip, which does not contain ethylenediamine, is expected to have less adverse effects and be easier to handle than aminophylline.","ja":"The effects of the speed of intravenous infusion on the pharmacokinetics of theophylline were studied in 9 healthy volunteers (Ex I). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip, Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and II, Cmax was 10.8 +/- 1.1 and 10.8 +/- 0.8 micrograms/ml, respectively. These Cmaxs were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The 90% confidence limits of the differences of mean values were within 80-120% and were 92.8-100.1% for Cmax, 99.7-105.3% for t1/2 and 100.2-104.4% for AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip (theophylline at 4.8 mg/kg) were bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II, no subjects had adverse effects and in Ex I no influence on ECG was seen. In addition, the convenience of Theodrip was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip were significantly shorter than those of aminophylline ampules. On the other hand, the adverse reactions to aminophylline resulting from hypersensitivity reactions to its ethylenediamine component have been reported. Theodrip consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore, Theodrip, which does not contain ethylenediamine, is expected to have less adverse effects and be easier to handle than aminophylline."},"publication_date":"2000-05","publication_name":{"en":"Methods and Findings in Experimental and Clinical Pharmacology","ja":"Methods and Findings in Experimental and Clinical Pharmacology"},"volume":"Vol.22","number":"No.4","starting_page":"247","ending_page":"252","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1358/mf.2000.22.4.584458"],"issn":["0379-0355"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.jstage.jst.go.jp/article/jjp/84/2/84_146/_article/-char/ja/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88478","label":"url"}],"paper_title":{"en":"Effect of endothelin-1(1-31) on human mesangial cell proliferation","ja":"Effect of endothelin-1(1-31) on human mesangial cell proliferation"},"authors":{"en":[{"name":"Yoshizumi Masanori"},{"name":"Kagami Shoji"},{"name":"Suzaki Yuki"},{"name":"Tsuchiya Koichiro"},{"name":"Houchi Hitoshi"},{"name":"Hisayama Tetsuhiro"},{"name":"Fukui Hiroyuki"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"吉栖 正典"},{"name":"香美 祥二"},{"name":"須崎 友紀"},{"name":"土屋 浩一郎"},{"name":"芳地 一"},{"name":"久山 哲廣"},{"name":"福井 裕行"},{"name":"玉置 俊晃"}]},"publication_date":"2000","publication_name":{"en":"The Japanese Journal of Pharmacology","ja":"The Japanese Journal of Pharmacology"},"volume":"Vol.84","number":"No.2","starting_page":"146","ending_page":"155","referee":true,"identifiers":{"issn":["0021-5198"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92587","label":"url"}],"paper_title":{"en":"Identification of PKC isozymes and effect of knockdown of PKC alpha by antisense oligodeoxynucleotide on iNOS expression via interleukin-1 receptor in vascular smooth muscle cells.","ja":"Identification of PKC isozymes and effect of knockdown of PKC alpha by antisense oligodeoxynucleotide on iNOS expression via interleukin-1 receptor in vascular smooth muscle cells."},"authors":{"en":[{"name":"Hisayama Tetsuhiro"},{"name":"Inomoto Mika"},{"name":"Hioki Yukari"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"久山 哲廣"},{"name":"猪本 美佳"},{"name":"日置 由加里"},{"name":"福井 裕行"}]},"publication_date":"1999-10","publication_name":{"en":"Folia Pharmacologica Japonica","ja":"Folia Pharmacologica Japonica"},"volume":"Vol.114","number":"No.1","starting_page":"86","ending_page":"91","referee":true,"identifiers":{"issn":["0015-5691"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://dx.doi.org/10.1016/S0090-6980(99)00021-0","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10482285","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132219","label":"url"}],"paper_title":{"en":"Effects of PAF on histamine H1 receptor mRNA expression in rat trigeminal ganglia","ja":"Effects of PAF on histamine H1 receptor mRNA expression in rat trigeminal ganglia"},"authors":{"en":[{"name":"Nakasaki Takashi"},{"name":"Masuyama Keisuke"},{"name":"Fukui Hiroyuki"},{"name":"Ogino Satoshi"},{"name":"Eura Masao"},{"name":"Samejima Yasuhiro"},{"name":"Ishikawa Takeru"},{"name":"Yumoto Eiji"}],"ja":[{"name":"Nakasaki Takashi"},{"name":"Masuyama Keisuke"},{"name":"福井 裕行"},{"name":"Ogino Satoshi"},{"name":"Eura Masao"},{"name":"Samejima Yasuhiro"},{"name":"Ishikawa Takeru"},{"name":"Yumoto Eiji"}]},"description":{"en":"The application of platelet-activating factor (PAF) to the nasal mucosa of humans has been shown to increase histamine-induced hyper-reactivity. To test the hypothesis that PAF acts by increasing the reactivity of sensory nerve endings in the nasal mucosa to histamine, we examined PAF-stimulated rat trigeminal nerve ganglion cells. We found that relatively low concentrations of PAF (10(-12)-10(-9) M) induced increased histamine H1 receptor mRNA expression. This increase appeared as early as 1 h after PAF stimulation, peaked at 4 h, and disappeared after 24 h. The PAF receptor antagonist WEB2086 inhibited the increased expression of histamine H1 receptor mRNA induced by PAF, suggesting that the effects of PAF are mediated by specific receptors. This PAF effect was abolished by actinomycin D, suggesting that PAF induces de novo transcription of histamine H1 and/or PAF receptor mRNA. PAF may be important in the hyper-responsiveness of nasal mucosa exposed to histamine.","ja":"The application of platelet-activating factor (PAF) to the nasal mucosa of humans has been shown to increase histamine-induced hyper-reactivity. To test the hypothesis that PAF acts by increasing the reactivity of sensory nerve endings in the nasal mucosa to histamine, we examined PAF-stimulated rat trigeminal nerve ganglion cells. We found that relatively low concentrations of PAF (10(-12)-10(-9) M) induced increased histamine H1 receptor mRNA expression. This increase appeared as early as 1 h after PAF stimulation, peaked at 4 h, and disappeared after 24 h. The PAF receptor antagonist WEB2086 inhibited the increased expression of histamine H1 receptor mRNA induced by PAF, suggesting that the effects of PAF are mediated by specific receptors. This PAF effect was abolished by actinomycin D, suggesting that PAF induces de novo transcription of histamine H1 and/or PAF receptor mRNA. PAF may be important in the hyper-responsiveness of nasal mucosa exposed to histamine."},"publication_date":"1999-08","publication_name":{"en":"Prostaglandins & Other Lipid Mediators","ja":"Prostaglandins & Other Lipid Mediators"},"volume":"Vol.58","number":"No.1","starting_page":"29","ending_page":"41","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0090-6980(99)00021-0"],"issn":["1098-8823"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://molpharm.aspetjournals.org/cgi/content/abstract/55/4/735?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&andorexactfulltext=and&searchid=1137474883560_1209&FIRSTINDEX=0&sortspec=relevance&firstpage=735&resourcetype=1&journalcode=molpharm","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10101032","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132217","label":"url"}],"paper_title":{"en":"Identification of Protein Kinase C Phosphorylation Sites Involved in Phorbol Ester-Induced Desensitization of the Histamine H1 Receptor","ja":"Identification of Protein Kinase C Phosphorylation Sites Involved in Phorbol Ester-Induced Desensitization of the Histamine H1 Receptor"},"authors":{"en":[{"name":"Fujimoto Katsumi"},{"name":"Ohta Kazumi"},{"name":"Kangawa Kenji"},{"name":"Kikkawa Ushio"},{"name":"Ogino Satoshi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Fujimoto Katsumi"},{"name":"Ohta Kazumi"},{"name":"Kangawa Kenji"},{"name":"Kikkawa Ushio"},{"name":"Ogino Satoshi"},{"name":"福井 裕行"}]},"description":{"en":"The histamine H1 receptor (H1R)-mediated signaling cascade is inhibited by phorbol ester-induced protein kinase C (PKC) activation. Cloning studies of the H1Rs have shown that several potential PKC phosphorylation sites are located in the third intracellular loop of H1R. To elucidate the molecular mechanism of PKC-mediated desensitization, we identified amino acid residues that are involved in the desensitization of the H1R. Two amino acid residues (Ser396, Ser398) were determined to be PKC phosphorylation sites by in vitro phosphorylation studies using a series of synthetic peptides. Treatment with phorbol ester decreased histamine-induced accumulation of inositol phosphates in Chinese hamster ovary cells expressing the H1R with a rightward shift in the EC50 value, which implies the uncoupling of the receptor from the G protein. Site-directed mutagenesis studies showed that substitution of alanine for Ser398 but not for Ser396 markedly attenuated the effect of phorbol ester, which suggests that the Ser398 residue was primarily involved in PKC-mediated desensitization.","ja":"The histamine H1 receptor (H1R)-mediated signaling cascade is inhibited by phorbol ester-induced protein kinase C (PKC) activation. Cloning studies of the H1Rs have shown that several potential PKC phosphorylation sites are located in the third intracellular loop of H1R. To elucidate the molecular mechanism of PKC-mediated desensitization, we identified amino acid residues that are involved in the desensitization of the H1R. Two amino acid residues (Ser396, Ser398) were determined to be PKC phosphorylation sites by in vitro phosphorylation studies using a series of synthetic peptides. Treatment with phorbol ester decreased histamine-induced accumulation of inositol phosphates in Chinese hamster ovary cells expressing the H1R with a rightward shift in the EC50 value, which implies the uncoupling of the receptor from the G protein. Site-directed mutagenesis studies showed that substitution of alanine for Ser398 but not for Ser396 markedly attenuated the effect of phorbol ester, which suggests that the Ser398 residue was primarily involved in PKC-mediated desensitization."},"publication_date":"1999-04","publication_name":{"en":"Molecular Pharmacology","ja":"Molecular Pharmacology"},"volume":"Vol.55","number":"No.4","starting_page":"735","ending_page":"742","languages":["eng"],"referee":true,"identifiers":{"issn":["0026-895X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://dx.doi.org/10.1016/S0169-328X(98)00346-5","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10095074","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132215","label":"url"}],"paper_title":{"en":"Gene expression of histamine H1 receptor in guinea pig primary sensory neurons: a relationship between H1 receptor mRNA-expressing neurons and peptidergic neurons","ja":"Gene expression of histamine H1 receptor in guinea pig primary sensory neurons: a relationship between H1 receptor mRNA-expressing neurons and peptidergic neurons"},"authors":{"en":[{"name":"Kashiba Hitoshi"},{"name":"Fukui Hiroyuki"},{"name":"Morikawa Yoshihiro"},{"name":"Senba Emiko"}],"ja":[{"name":"Kashiba Hitoshi"},{"name":"福井 裕行"},{"name":"Morikawa Yoshihiro"},{"name":"Senba Emiko"}]},"description":{"en":"Pharmacological studies have suggested that a subgroup of primary sensory neurons is responsive to histamine via the histamine H1 receptor. We addressed this issue using in situ hybridization histochemistry with a cRNA probe for the guinea pig H1 receptor gene. About 15% of the trigeminal and lumber dorsal root ganglion (DRG) neurons, but none of nodose ganglion neurons, were intensely labeled with this probe. The H1 receptor mRNA-positive neurons were exclusively small in size, and were demonstrated to give rise to unmyelinated fibers by ultrastructural analysis of isolectin B4-labeling. However, the H1 receptor mRNA-expressing DRG neurons were not immunoreactive to substance P (SP) and calcitonin gene-related peptide (CGRP). A marked increase in the number of mRNA-positive DRG neurons were observed 1-5 days after a crush injury of the sciatic nerve (3-4-fold of the control value). These neurons turned mRNA-positive after the nerve crush were also mainly small-sized. The mRNA signals were detected in many peptidergic (SP/CGRP) neurons, in contrast to the normal state. On the other hand, in the neurons which showed intense labeling in the normal condition, the mRNA signals were down-regulated. These results suggest that primary sensory neurons include two kinds of H1 receptor-expressing sensory neurons, one expressing H1 receptor mRNAs in the normal state and the other up-regulating the mRNAs following the peripheral nerve damage.","ja":"Pharmacological studies have suggested that a subgroup of primary sensory neurons is responsive to histamine via the histamine H1 receptor. We addressed this issue using in situ hybridization histochemistry with a cRNA probe for the guinea pig H1 receptor gene. About 15% of the trigeminal and lumber dorsal root ganglion (DRG) neurons, but none of nodose ganglion neurons, were intensely labeled with this probe. The H1 receptor mRNA-positive neurons were exclusively small in size, and were demonstrated to give rise to unmyelinated fibers by ultrastructural analysis of isolectin B4-labeling. However, the H1 receptor mRNA-expressing DRG neurons were not immunoreactive to substance P (SP) and calcitonin gene-related peptide (CGRP). A marked increase in the number of mRNA-positive DRG neurons were observed 1-5 days after a crush injury of the sciatic nerve (3-4-fold of the control value). These neurons turned mRNA-positive after the nerve crush were also mainly small-sized. The mRNA signals were detected in many peptidergic (SP/CGRP) neurons, in contrast to the normal state. On the other hand, in the neurons which showed intense labeling in the normal condition, the mRNA signals were down-regulated. These results suggest that primary sensory neurons include two kinds of H1 receptor-expressing sensory neurons, one expressing H1 receptor mRNAs in the normal state and the other up-regulating the mRNAs following the peripheral nerve damage."},"publication_date":"1999-03-20","publication_name":{"en":"Brain Research. Molecular Brain Research","ja":"Brain Research. Molecular Brain Research"},"volume":"Vol.66","number":"No.1-2","starting_page":"24","ending_page":"34","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0169-328X(98)00346-5"],"issn":["0169-328X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.blackwell-synergy.com/doi/abs/10.1046/j.1460-9568.1998.00240.x","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9749757","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132214","label":"url"}],"paper_title":{"en":"Postnatal expression of H1receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures","ja":"Postnatal expression of H1receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures"},"authors":{"en":[{"name":"Lintunen Minnamaija"},{"name":"Sallmen Tina"},{"name":"Karlstedt Kaj"},{"name":"Fukui Hiroyuki"},{"name":"Eriksson S. Krister"},{"name":"Panula Pertti"}],"ja":[{"name":"Lintunen Minnamaija"},{"name":"Sallmen Tina"},{"name":"Karlstedt Kaj"},{"name":"福井 裕行"},{"name":"Eriksson S. Krister"},{"name":"Panula Pertti"}]},"description":{"en":"Histamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1-receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of L-histidine decarboxylase (HDC) in the two pools was revealed. H1-receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1-receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1-receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1-receptor expression. Systemic kainic acid administration induced increased expression of H1-receptor mRNA in the caudate-putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1-CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1-receptor, is involved in the regulation of seizure activity in the brain.","ja":"Histamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1-receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of L-histidine decarboxylase (HDC) in the two pools was revealed. H1-receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1-receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1-receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1-receptor expression. Systemic kainic acid administration induced increased expression of H1-receptor mRNA in the caudate-putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1-CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1-receptor, is involved in the regulation of seizure activity in the brain."},"publication_date":"1998-07","publication_name":{"en":"The European Journal of Neuroscience","ja":"The European Journal of Neuroscience"},"volume":"Vol.10","number":"No.7","starting_page":"2287","ending_page":"2301","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1046/j.1460-9568.1998.00240.x"],"issn":["0953-816X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www3.interscience.wiley.com/cgi-bin/abstract/31418/ABSTRACT","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9550146","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132210","label":"url"}],"paper_title":{"en":"In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain","ja":"In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain"},"authors":{"en":[{"name":"Kinnunen Anu"},{"name":"Lintunen Minnamaija"},{"name":"Karlstedt Kaj"},{"name":"Fukui Hiroyuki"},{"name":"Panula Pertti"}],"ja":[{"name":"Kinnunen Anu"},{"name":"Lintunen Minnamaija"},{"name":"Karlstedt Kaj"},{"name":"福井 裕行"},{"name":"Panula Pertti"}]},"description":{"en":"In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak.","ja":"In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak."},"publication_date":"1998-04-27","publication_name":{"en":"The Journal of Comparative Neurology","ja":"The Journal of Comparative Neurology"},"volume":"Vol.394","number":"No.1","starting_page":"127","ending_page":"137","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/(SICI)1096-9861(19980427)394:1<127::AID-CNE10>3.0.CO;2-L"],"issn":["0021-9967"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://dx.doi.org/10.1016/S0014-2999(97)01620-8","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9593602","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132208","label":"url"}],"paper_title":{"en":"Unique binding pocket for KW-4679 in the histamine H1 receptor","ja":"Unique binding pocket for KW-4679 in the histamine H1 receptor"},"authors":{"en":[{"name":"Nonaka Hiromi"},{"name":"Otaki Shizuo"},{"name":"Ohshima Etsuo"},{"name":"Kono Motomichi"},{"name":"Kase Hiroshi"},{"name":"Ohta Kazumi"},{"name":"Fukui Hiroyuki"},{"name":"Ichimura Michio"}],"ja":[{"name":"Nonaka Hiromi"},{"name":"Otaki Shizuo"},{"name":"Ohshima Etsuo"},{"name":"Kono Motomichi"},{"name":"Kase Hiroshi"},{"name":"Ohta Kazumi"},{"name":"福井 裕行"},{"name":"Ichimura Michio"}]},"description":{"en":"The histamine H1 receptor has an aspartate (Asp) residue in transmembrane helix 3 (TM3), which is well-conserved among biogenic amine receptors. The Asp residue is one of the most crucial amino acids for ligand binding. The tested histamine H1 receptor antagonists with tri- and tetracyclic structures were not selective for histamine H1 receptors and showed affinity for several other biogenic amine receptors. In contrast, KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b, e]oxepin-2-acetic acid hydrochloride), a tricyclic compound, was a selective histamine H1 receptor antagonist. [3H]KW-4679 had high affinity (Kd value of 2.5 +/- 0.12 nM) for wild-type human histamine H1 receptors. In the [3H]KW-4679 binding assay, replacement of Asp107 by alanine by site-directed mutagenesis greatly reduced the affinities (280-2100-fold) of tri- and tetracyclic compounds, whereas this mutation led to a comparatively small reduction (14-fold) in KW-4679 affinity. These results demonstrate that the tested tri- and tetracyclic histamine H1 receptor antagonists which have a tight interaction with the Asp residue are not selective for the histamine H1 receptor. Furthermore, the high selectivity of KW-4679 might be explained by a unique binding pocket, which consists of the Asp residue and other acceptor sites, in the histamine H1 receptor.","ja":"The histamine H1 receptor has an aspartate (Asp) residue in transmembrane helix 3 (TM3), which is well-conserved among biogenic amine receptors. The Asp residue is one of the most crucial amino acids for ligand binding. The tested histamine H1 receptor antagonists with tri- and tetracyclic structures were not selective for histamine H1 receptors and showed affinity for several other biogenic amine receptors. In contrast, KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b, e]oxepin-2-acetic acid hydrochloride), a tricyclic compound, was a selective histamine H1 receptor antagonist. [3H]KW-4679 had high affinity (Kd value of 2.5 +/- 0.12 nM) for wild-type human histamine H1 receptors. In the [3H]KW-4679 binding assay, replacement of Asp107 by alanine by site-directed mutagenesis greatly reduced the affinities (280-2100-fold) of tri- and tetracyclic compounds, whereas this mutation led to a comparatively small reduction (14-fold) in KW-4679 affinity. These results demonstrate that the tested tri- and tetracyclic histamine H1 receptor antagonists which have a tight interaction with the Asp residue are not selective for the histamine H1 receptor. Furthermore, the high selectivity of KW-4679 might be explained by a unique binding pocket, which consists of the Asp residue and other acceptor sites, in the histamine H1 receptor."},"publication_date":"1998-03-12","publication_name":{"en":"European Journal of Pharmacology","ja":"European Journal of Pharmacology"},"volume":"Vol.345","number":"No.1","starting_page":"111","ending_page":"117","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0014-2999(97)01620-8"],"issn":["0014-2999"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=132207","label":"url"}],"paper_title":{"en":"Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors","ja":"Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors"},"authors":{"en":[{"name":"Ohuchi Y"},{"name":"Yanai Kazuhiko"},{"name":"Sakurai Eiko"},{"name":"Fukui Hiroyuki"},{"name":"Yanagisawa T"},{"name":"Watanabe Takehiko"}],"ja":[{"name":"Ohuchi Y"},{"name":"Yanai Kazuhiko"},{"name":"Sakurai Eiko"},{"name":"福井 裕行"},{"name":"Yanagisawa T"},{"name":"Watanabe Takehiko"}]},"publication_date":"1998-02-01","publication_name":{"en":"International Journal of Molecular Medicine","ja":"International Journal of Molecular Medicine"},"volume":"Vol.1","number":"No.2","starting_page":"355","ending_page":"360","languages":["eng"],"referee":true,"identifiers":{"issn":["1107-3756"]},"published_paper_type":"scientific_journal"}}
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{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162510","label":"url"}],"paper_title":{"en":"Expression and characterization of the bovine histamine H1 receptor in cDNA-transfected C6 astroglioma cells.","ja":"Expression and characterization of the bovine histamine H1 receptor in cDNA-transfected C6 astroglioma cells."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Ito Seiji"},{"name":"Shevchenko VI"},{"name":"Nagasawa Yasuyuki"},{"name":"Yamashita Masakatsu"},{"name":"Imamura Ikuo"},{"name":"Horio Yoshiyuki"},{"name":"Fujimoto Katsumi"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"水口 博之"},{"name":"Ito Seiji"},{"name":"Shevchenko VI"},{"name":"Nagasawa Yasuyuki"},{"name":"Yamashita Masakatsu"},{"name":"Imamura Ikuo"},{"name":"Horio Yoshiyuki"},{"name":"Fujimoto Katsumi"},{"name":"福井 裕行"}]},"publication_date":"1994","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.115","number":"No.6","starting_page":"1155","ending_page":"1161","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-924X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162499","label":"url"}],"paper_title":{"en":"Tissue distribution of histamine N-methyltransferase-like immunoreactivity in rodents.","ja":"Tissue distribution of histamine N-methyltransferase-like immunoreactivity in rodents."},"authors":{"en":[{"name":"Takemura Motohiko"},{"name":"Imamura Ikuo"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Yamatodani Atsushi"}],"ja":[{"name":"Takemura Motohiko"},{"name":"Imamura Ikuo"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"Yamatodani Atsushi"}]},"publication_date":"1994","publication_name":{"en":"Life Sciences","ja":"Life Sciences"},"volume":"Vol.54","number":"No.15","starting_page":"1059","ending_page":"1071","languages":["eng"],"referee":true,"identifiers":{"issn":["0024-3205"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/8111144","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163833","label":"url"}],"paper_title":{"en":"Role of nucleosides and nucleotide mixture in intestinal mucosal growth under total parenteral nutrition.","ja":"Role of nucleosides and nucleotide mixture in intestinal mucosal growth under total parenteral nutrition."},"authors":{"en":[{"name":"Tsujinaka T"},{"name":"Iijima S"},{"name":"Kido Y"},{"name":"Homma T"},{"name":"Ebisui C"},{"name":"Kan K"},{"name":"Imamura I"},{"name":"Fukui Hiroyuki"},{"name":"Mori T"}],"ja":[{"name":"Tsujinaka T"},{"name":"Iijima S"},{"name":"Kido Y"},{"name":"Homma T"},{"name":"Ebisui C"},{"name":"Kan K"},{"name":"Imamura I"},{"name":"福井 裕行"},{"name":"Mori T"}]},"description":{"en":"The preventive effect of a mixture of nucleosides and a nucleotide (OG-VI) on total parenteral nutrition (TPN)-associated gut mucosal atrophy was investigated. Male Wistar rats were randomly divided into two groups. The TPN group (n = 11) received a standard TPN diet (250 kcal and 1.78 g nitrogen.kg-1.day-1) for 6 days; the TPN + OG-VI group (n = 10) received OG-VI (2.5 ml.kg-1.day-1) in addition to the standard TPN solution for 6 days. To obtain information on a normal fed condition of the intestine, another 10 rats were maintained on oral rat chow for 6 days. Compared with the TPN group, mucosal wet weights in the jejunum (22.8 +/- 1.8 vs. 20.5 +/- 2.0 mg/cm) and the ileum (19.4 +/- 2.2 vs. 16.8 +/- 2.3 mg/cm) were significantly greater in the TPN + OG-VI group. Likewise, diamine oxidase activities in the jejunum (13.7 +/- 4.27 vs. 8.02 +/- 3.40 nmol.min-1.cm-1) and the ileum (33.9 +/- 6.89 vs. 25.9 +/- 7.93 nmol.min-1.cm-1) were significantly higher in the TPN + OG-VI group. Moreover, the bromodeoxyuridine labeling index in the TPN + OG-VI group (36.9 +/- 4.30%) was significantly higher than in the TPN group (31.0 +/- 3.03%). The addition of OG-VI to the standard TPN diet improved mucosal growth and maturity by increasing the proliferating activity of crypt cells. External provision of purines and pyrimidines may be necessary to sustain mucosal function during TPN.","ja":"The preventive effect of a mixture of nucleosides and a nucleotide (OG-VI) on total parenteral nutrition (TPN)-associated gut mucosal atrophy was investigated. Male Wistar rats were randomly divided into two groups. The TPN group (n = 11) received a standard TPN diet (250 kcal and 1.78 g nitrogen.kg-1.day-1) for 6 days; the TPN + OG-VI group (n = 10) received OG-VI (2.5 ml.kg-1.day-1) in addition to the standard TPN solution for 6 days. To obtain information on a normal fed condition of the intestine, another 10 rats were maintained on oral rat chow for 6 days. Compared with the TPN group, mucosal wet weights in the jejunum (22.8 +/- 1.8 vs. 20.5 +/- 2.0 mg/cm) and the ileum (19.4 +/- 2.2 vs. 16.8 +/- 2.3 mg/cm) were significantly greater in the TPN + OG-VI group. Likewise, diamine oxidase activities in the jejunum (13.7 +/- 4.27 vs. 8.02 +/- 3.40 nmol.min-1.cm-1) and the ileum (33.9 +/- 6.89 vs. 25.9 +/- 7.93 nmol.min-1.cm-1) were significantly higher in the TPN + OG-VI group. Moreover, the bromodeoxyuridine labeling index in the TPN + OG-VI group (36.9 +/- 4.30%) was significantly higher than in the TPN group (31.0 +/- 3.03%). The addition of OG-VI to the standard TPN diet improved mucosal growth and maturity by increasing the proliferating activity of crypt cells. External provision of purines and pyrimidines may be necessary to sustain mucosal function during TPN."},"publication_date":"1993-11","publication_name":{"en":"Nutrition","ja":"Nutrition"},"volume":"Vol.9","number":"No.6","starting_page":"532","ending_page":"535","languages":["eng"],"referee":true,"identifiers":{"issn":["0899-9007"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/8216261","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163836","label":"url"}],"paper_title":{"en":"High stable expression of the bovine histamine H1-receptor coupled to [Ca2+]i mobilization in CHO-K1 cells.","ja":"High stable expression of the bovine histamine H1-receptor coupled to [Ca2+]i mobilization in CHO-K1 cells."},"authors":{"en":[{"name":"Iredale PA"},{"name":"Fukui Hiroyuki"},{"name":"Hill SJ"}],"ja":[{"name":"Iredale PA"},{"name":"福井 裕行"},{"name":"Hill SJ"}]},"description":{"en":"The bovine H1-receptor DNA was transfected into Chinese hamster ovary cells (CHO-K1) using an expression vector. Binding studies revealed very high expression levels of the receptor which was found to have a Kd for [3H]-mepyramine of 1 nM. Addition of histamine resulted in a concentration-dependent increase in intracellular calcium which was found to involve both release from intracellular stores and entry across the plasma membrane. Furthermore, the response demonstrated the pharmacological characteristics of an H1-receptor-mediated event. Thus, we present the first report of the high, functional expression of the bovine H1-receptor coupled to mobilisation of intracellular calcium in CHO-K1 cells.","ja":"The bovine H1-receptor DNA was transfected into Chinese hamster ovary cells (CHO-K1) using an expression vector. Binding studies revealed very high expression levels of the receptor which was found to have a Kd for [3H]-mepyramine of 1 nM. Addition of histamine resulted in a concentration-dependent increase in intracellular calcium which was found to involve both release from intracellular stores and entry across the plasma membrane. Furthermore, the response demonstrated the pharmacological characteristics of an H1-receptor-mediated event. Thus, we present the first report of the high, functional expression of the bovine H1-receptor coupled to mobilisation of intracellular calcium in CHO-K1 cells."},"publication_date":"1993-09-30","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.195","number":"No.3","starting_page":"1294","ending_page":"1300","languages":["eng"],"referee":true,"identifiers":{"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/8282735","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163845","label":"url"}],"paper_title":{"en":"Molecular cloning of guinea-pig histamine H1 receptor gene.","ja":"Molecular cloning of guinea-pig histamine H1 receptor gene."},"authors":{"en":[{"name":"Horio Yoshiyuki"},{"name":"Mori Yasutake"},{"name":"Higuchi I"},{"name":"Fujimoto Katsumi"},{"name":"Ito Seiji"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Horio Yoshiyuki"},{"name":"Mori Yasutake"},{"name":"Higuchi I"},{"name":"Fujimoto Katsumi"},{"name":"Ito Seiji"},{"name":"福井 裕行"}]},"description":{"en":"The histamine H1 receptor gene was isolated from a guinea-pig gene library. The gene contains no introns and encodes a protein of 488 amino acid residues. The structure of the guinea-pig histamine H1 receptor is predicted to contain seven putative transmembrane regions, which are similar to those of receptors coupling with GTP binding proteins. Although the third intracellular domain, the predicted binding site for the GTP binding protein, showed only 50% identity with those of the bovine and rat H1 receptors, the expressed guinea-pig H1 receptor was fully able to bind with [3H]mepyramine. Northern blot analysis indicated that the cerebrum, cerebellum, lung, adrenal, intestine, and heart expressed 3.3 kb guinea-pig H1 receptor mRNA. Expression of histamine H1 mRNA of guinea-pig peripheral organs was greater than that of rat organs, suggesting the high sensitivity of guinea-pig organs as to histamine is due to the contents of histamine H1 receptor mRNA. In addition, the lung, adrenal, intestine, and heart expressed 3.9 kb mRNA. In situ hybridization showed that the hippocampus, cerebral cortex, thalamus, and granular layer of the cerebellum each contained a large amount of histamine H1 receptors. Southern blot analysis showed that there was another gene quite similar to the cloned histamine H1 receptor gene.","ja":"The histamine H1 receptor gene was isolated from a guinea-pig gene library. The gene contains no introns and encodes a protein of 488 amino acid residues. The structure of the guinea-pig histamine H1 receptor is predicted to contain seven putative transmembrane regions, which are similar to those of receptors coupling with GTP binding proteins. Although the third intracellular domain, the predicted binding site for the GTP binding protein, showed only 50% identity with those of the bovine and rat H1 receptors, the expressed guinea-pig H1 receptor was fully able to bind with [3H]mepyramine. Northern blot analysis indicated that the cerebrum, cerebellum, lung, adrenal, intestine, and heart expressed 3.3 kb guinea-pig H1 receptor mRNA. Expression of histamine H1 mRNA of guinea-pig peripheral organs was greater than that of rat organs, suggesting the high sensitivity of guinea-pig organs as to histamine is due to the contents of histamine H1 receptor mRNA. In addition, the lung, adrenal, intestine, and heart expressed 3.9 kb mRNA. In situ hybridization showed that the hippocampus, cerebral cortex, thalamus, and granular layer of the cerebellum each contained a large amount of histamine H1 receptors. Southern blot analysis showed that there was another gene quite similar to the cloned histamine H1 receptor gene."},"publication_date":"1993-09","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.114","number":"No.3","starting_page":"408","ending_page":"414","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-924X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/7678492","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163860","label":"url"}],"paper_title":{"en":"Genomic cloning of the rat histamine H1 receptor.","ja":"Genomic cloning of the rat histamine H1 receptor."},"authors":{"en":[{"name":"Fujimoto, Katsumi"},{"name":"Horio, Yoshiyuki"},{"name":"Sugama, Kazushige"},{"name":"Ito, Seiji"},{"name":"Liu, Y-Q"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Fujimoto, Katsumi"},{"name":"Horio, Yoshiyuki"},{"name":"Sugama, Kazushige"},{"name":"Ito, Seiji"},{"name":"Liu, Y-Q"},{"name":"福井 裕行"}]},"description":{"en":"A rat histamine H1 receptor gene which lacked introns was isolated from a rat genomic library using recently cloned bovine histamine H1 receptor cDNA [Yamashita et al., Proc. Natl. Acad. Sci. USA, 88, 11515-11519 (1991)]. The receptor protein deduced from this isolated gene was composed of 486 amino acids and showed characteristic properties of G protein-coupled receptors. At the 5'-flanking region of the receptor gene, we have located potential TATA box sequences and consensus sequences for the glucocorticoid response element and AP-2 element. After being subcloned into a mammalian expression vector, the isolated gene was transfected to C6 glioma cells. These cells showed significant binding toward [3H]mepyramine. The binding was inhibited by H1 antagonists or histamine. The mode of this binding was comparable to the binding of membranes derived from rat tissues toward [3H]mepyramine. Northern blot analysis detected a 3.0 kb nucleotide band for histamine H1 receptor mRNAs from rat brain and small intestine when these mRNAs were hybridized with the isolated rat H1 gene. The present results demonstrate the isolation of the rat histamine H1 receptor gene.","ja":"A rat histamine H1 receptor gene which lacked introns was isolated from a rat genomic library using recently cloned bovine histamine H1 receptor cDNA [Yamashita et al., Proc. Natl. Acad. Sci. USA, 88, 11515-11519 (1991)]. The receptor protein deduced from this isolated gene was composed of 486 amino acids and showed characteristic properties of G protein-coupled receptors. At the 5'-flanking region of the receptor gene, we have located potential TATA box sequences and consensus sequences for the glucocorticoid response element and AP-2 element. After being subcloned into a mammalian expression vector, the isolated gene was transfected to C6 glioma cells. These cells showed significant binding toward [3H]mepyramine. The binding was inhibited by H1 antagonists or histamine. The mode of this binding was comparable to the binding of membranes derived from rat tissues toward [3H]mepyramine. Northern blot analysis detected a 3.0 kb nucleotide band for histamine H1 receptor mRNAs from rat brain and small intestine when these mRNAs were hybridized with the isolated rat H1 gene. The present results demonstrate the isolation of the rat histamine H1 receptor gene."},"publication_date":"1993-01-15","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.190","number":"No.1","starting_page":"294","ending_page":"301","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1006/bbrc.1993.1045"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163858","label":"url"}],"paper_title":{"en":"Histamine content, synthesis and degradation in human nasal mucosa.","ja":"Histamine content, synthesis and degradation in human nasal mucosa."},"authors":{"en":[{"name":"Abe, Yoshiyuki"},{"name":"Ogino, Satoshi"},{"name":"Irifune, Morihiro"},{"name":"Imamura, Ikuo"},{"name":"Fukui Hiroyuki"},{"name":"Wada, Hiroshi"},{"name":"Matsunaga, Tohru"}],"ja":[{"name":"Abe, Yoshiyuki"},{"name":"Ogino, Satoshi"},{"name":"Irifune, Morihiro"},{"name":"Imamura, Ikuo"},{"name":"福井 裕行"},{"name":"Wada, Hiroshi"},{"name":"Matsunaga, Tohru"}]},"publication_date":"1993","publication_name":{"en":"Clinical Experimental Allergy","ja":"Clinical Experimental Allergy"},"volume":"Vol.23","starting_page":"132","ending_page":"136","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163855","label":"url"}],"paper_title":{"en":"Histamine content, synthesis and degradation on nasal mucosa and lung of guinea-pig treated with toluene diisocyanate (TDI).","ja":"Histamine content, synthesis and degradation on nasal mucosa and lung of guinea-pig treated with toluene diisocyanate (TDI)."},"authors":{"en":[{"name":"Abe, Yoshiyuki"},{"name":"Ogino, Satoshi"},{"name":"Irifune, Morihiro"},{"name":"Imamura, Ikuo"},{"name":"Liu, Y-Q"},{"name":"Fukui Hiroyuki"},{"name":"Matsunaga, Tohru"}],"ja":[{"name":"Abe, Yoshiyuki"},{"name":"Ogino, Satoshi"},{"name":"Irifune, Morihiro"},{"name":"Imamura, Ikuo"},{"name":"Liu, Y-Q"},{"name":"福井 裕行"},{"name":"Matsunaga, Tohru"}]},"publication_date":"1993","publication_name":{"en":"Clinical Experimental Allergy","ja":"Clinical Experimental Allergy"},"volume":"Vol.23","starting_page":"512","ending_page":"517","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163852","label":"url"}],"paper_title":{"en":"Molecular cloning of guinea-pig histamine H1 receptor gene.","ja":"Molecular cloning of guinea-pig histamine H1 receptor gene."},"authors":{"en":[{"name":"Ogino S"},{"name":"Abe Y"},{"name":"Irifune M"},{"name":"Harada T"},{"name":"Imamura I"},{"name":"Fukui Hiroyuki"},{"name":"Matsunaga T"}],"ja":[{"name":"Ogino S"},{"name":"Abe Y"},{"name":"Irifune M"},{"name":"Harada T"},{"name":"Imamura I"},{"name":"福井 裕行"},{"name":"Matsunaga T"}]},"publication_date":"1993","publication_name":{"en":"Otology Rhinology Laryngology","ja":"Otology Rhinology Laryngology"},"volume":"Vol.102","starting_page":"152","ending_page":"156","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163844","label":"url"}],"paper_title":{"en":"Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat.","ja":"Somatostatin inhibits gastrin-induced histamine secretion and synthesis in the rat."},"authors":{"en":[{"name":"Kondo S"},{"name":"Shinomura Y"},{"name":"Kanayama S"},{"name":"Kawabata S"},{"name":"Miyazaki Y"},{"name":"Imamura I"},{"name":"Fukui Hiroyuki"},{"name":"Wada H"},{"name":"Matsuzawa Y"}],"ja":[{"name":"Kondo S"},{"name":"Shinomura Y"},{"name":"Kanayama S"},{"name":"Kawabata S"},{"name":"Miyazaki Y"},{"name":"Imamura I"},{"name":"福井 裕行"},{"name":"Wada H"},{"name":"Matsuzawa Y"}]},"publication_date":"1993","volume":"Vol.48","starting_page":"373","ending_page":"380","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163873","label":"url"}],"paper_title":{"en":"Vasopressin-induced changes in brain histamine and H-1 receptors.","ja":"Vasopressin-induced changes in brain histamine and H-1 receptors."},"authors":{"en":[{"name":"Cacabelos Ramon"},{"name":"Niigawa H"},{"name":"Yamatodani Atsushi"},{"name":"Fukui Hiroyuki"},{"name":"Nishimura T"},{"name":"Wada Hiroshi"}],"ja":[{"name":"Cacabelos Ramon"},{"name":"Niigawa H"},{"name":"Yamatodani Atsushi"},{"name":"福井 裕行"},{"name":"Nishimura T"},{"name":"Wada Hiroshi"}]},"publication_date":"1992","publication_name":{"en":"Experimental Clinical Endocrinology","ja":"Experimental Clinical Endocrinology"},"volume":"Vol.11","starting_page":"37","ending_page":"44","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163870","label":"url"}],"paper_title":{"en":"Effect of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs.","ja":"Effect of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs."},"authors":{"en":[{"name":"Abe, Yoshiyuki"},{"name":"Takeda Noriaki"},{"name":"Irifune, Morihiro"},{"name":"Ogino, Satoshi"},{"name":"Kalubi B"},{"name":"Imamura, Ikuo"},{"name":"Fukui Hiroyuki"},{"name":"Wada, Hiroshi"},{"name":"Matsunaga, Tohru"}],"ja":[{"name":"Abe, Yoshiyuki"},{"name":"武田 憲昭"},{"name":"Irifune, Morihiro"},{"name":"Ogino, Satoshi"},{"name":"Kalubi B"},{"name":"Imamura, Ikuo"},{"name":"福井 裕行"},{"name":"Wada, Hiroshi"},{"name":"Matsunaga, Tohru"}]},"publication_date":"1992","publication_name":{"en":"Acta Otolaryngolica (Stockholm)","ja":"Acta Otolaryngolica (Stockholm)"},"volume":"Vol.112","starting_page":"703","ending_page":"709","languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/1324890","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163865","label":"url"}],"paper_title":{"en":"Type-1 and type-2 astrocytes are distinct targets for prostaglandins D2, E2 and F2α.","ja":"Type-1 and type-2 astrocytes are distinct targets for prostaglandins D2, E2 and F2α."},"authors":{"en":[{"name":"Ito Seiji"},{"name":"Sugama Kazushige"},{"name":"Inagaki Naoyuki"},{"name":"Fukui Hiroyuki"},{"name":"Giles H"},{"name":"Wada Hiroshi"},{"name":"Hayaishi Osamu"}],"ja":[{"name":"Ito Seiji"},{"name":"Sugama Kazushige"},{"name":"Inagaki Naoyuki"},{"name":"福井 裕行"},{"name":"Giles H"},{"name":"Wada Hiroshi"},{"name":"Hayaishi Osamu"}]},"description":{"en":"Accumulating evidence has revealed that astrocytes are potential targets for various neurotransmitters. Here we investigated the effects of prostaglandins (PGs) on signal transduction in purified primary cultures of rat type-1 and type-2 astrocytes. PGF2 alpha, PGD2, and 9 alpha,11 beta-PGF2, a metabolite of PGD2 and a stereoisomer of PGF2 alpha, evoked a rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) in type-1, but not in type-2, astrocytes. STA2, a stable analogue of thromboxane A2, was less effective, and PGE2 showed little effect. The PG-induced rise in [Ca2+]i was not blocked by an antagonist of either PGD2 receptor or thromboxane A2 receptor. PGF2 alpha and 9 alpha,11 beta-PGF2 stimulated rapid formation of inositol trisphosphate followed by inositol bisphosphate and inositol monophosphate. On the other hand, PGE2 increased the intracellular level of cyclic AMP in type-2 astrocytes, rather than in type-1 astrocytes. The potency of PGs for cyclic AMP formation was in the following order: PGE2 greater than PGE1 greater than or equal to STA2 much greater than iloprost, a stable analogue of PGI2. PGD2 and PGF2 alpha had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF2 alpha receptors, the activation of which leads to phosphoinositide metabolism and [Ca2+]i elevation, whereas type-2 astrocytes possess PGE receptors that are linked to cyclic AMP formation.","ja":"Accumulating evidence has revealed that astrocytes are potential targets for various neurotransmitters. Here we investigated the effects of prostaglandins (PGs) on signal transduction in purified primary cultures of rat type-1 and type-2 astrocytes. PGF2 alpha, PGD2, and 9 alpha,11 beta-PGF2, a metabolite of PGD2 and a stereoisomer of PGF2 alpha, evoked a rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) in type-1, but not in type-2, astrocytes. STA2, a stable analogue of thromboxane A2, was less effective, and PGE2 showed little effect. The PG-induced rise in [Ca2+]i was not blocked by an antagonist of either PGD2 receptor or thromboxane A2 receptor. PGF2 alpha and 9 alpha,11 beta-PGF2 stimulated rapid formation of inositol trisphosphate followed by inositol bisphosphate and inositol monophosphate. On the other hand, PGE2 increased the intracellular level of cyclic AMP in type-2 astrocytes, rather than in type-1 astrocytes. The potency of PGs for cyclic AMP formation was in the following order: PGE2 greater than PGE1 greater than or equal to STA2 much greater than iloprost, a stable analogue of PGI2. PGD2 and PGF2 alpha had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF2 alpha receptors, the activation of which leads to phosphoinositide metabolism and [Ca2+]i elevation, whereas type-2 astrocytes possess PGE receptors that are linked to cyclic AMP formation."},"publication_date":"1992","publication_name":{"en":"Glia","ja":"Glia"},"volume":"Vol.6","number":"No.1","starting_page":"67","ending_page":"74","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/glia.440060109"],"issn":["0894-1491"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162486","label":"url"}],"paper_title":{"en":"Re-examination of [3H]mepyramine binding assay for histamine H1 receptor using quinine.","ja":"Re-examination of [3H]mepyramine binding assay for histamine H1 receptor using quinine."},"authors":{"en":[{"name":"Liu YeQi"},{"name":"Horio Yoshiyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fujimoto Katsumi"},{"name":"Imamura Ikuo"},{"name":"Abe Yoshiyuki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Liu YeQi"},{"name":"Horio Yoshiyuki"},{"name":"水口 博之"},{"name":"Fujimoto Katsumi"},{"name":"Imamura Ikuo"},{"name":"Abe Yoshiyuki"},{"name":"福井 裕行"}]},"publication_date":"1992","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.189","number":"No.1","starting_page":"378","ending_page":"384","languages":["eng"],"referee":true,"identifiers":{"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162477","label":"url"}],"paper_title":{"en":"Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells.","ja":"Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells."},"authors":{"en":[{"name":"Takemura Motohiko"},{"name":"Tanaka Tatsuya"},{"name":"Taguchi Yoshitaka"},{"name":"Imamura Ikuo"},{"name":"Mizuguchi Hiroyuki"},{"name":"Kuroda Masao"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Takemura Motohiko"},{"name":"Tanaka Tatsuya"},{"name":"Taguchi Yoshitaka"},{"name":"Imamura Ikuo"},{"name":"水口 博之"},{"name":"Kuroda Masao"},{"name":"福井 裕行"}]},"publication_date":"1992","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.267","number":"No.22","starting_page":"15687","ending_page":"15691","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-9258"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162469","label":"url"}],"paper_title":{"en":"Expression cloning of a cDNA encoding the bovine histamine H1 receptor.","ja":"Expression cloning of a cDNA encoding the bovine histamine H1 receptor."},"authors":{"en":[{"name":"Yamashita Masakatsu"},{"name":"Fukui Hiroyuki"},{"name":"Sugama Kazushige"},{"name":"Horio Yoshiyuki"},{"name":"Ito Seiji"},{"name":"Mizuguchi Hiroyuki"},{"name":"Wada Hiroshi"}],"ja":[{"name":"Yamashita Masakatsu"},{"name":"福井 裕行"},{"name":"Sugama Kazushige"},{"name":"Horio Yoshiyuki"},{"name":"Ito Seiji"},{"name":"水口 博之"},{"name":"Wada Hiroshi"}]},"publication_date":"1991","publication_name":{"en":"Proceedings of the National Academy of Sciences of the United States of America","ja":"Proceedings of the National Academy of Sciences of the United States of America"},"volume":"Vol.88","number":"No.24","starting_page":"11515","ending_page":"11519","languages":["eng"],"referee":true,"identifiers":{"issn":["0027-8424"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162464","label":"url"}],"paper_title":{"en":"Adenosine induces System A amino acid transport in cultured rat hepatocytes.","ja":"Adenosine induces System A amino acid transport in cultured rat hepatocytes."},"authors":{"en":[{"name":"Kiyokawa Hiroaki"},{"name":"Fukui Hiroyuki"},{"name":"Mizuguchi Hiroyuki"},{"name":"Kubo Akiharu"},{"name":"Kono Norio"},{"name":"Tarui Seiichiro"},{"name":"Wada Hiroshi"}],"ja":[{"name":"Kiyokawa Hiroaki"},{"name":"福井 裕行"},{"name":"水口 博之"},{"name":"Kubo Akiharu"},{"name":"Kono Norio"},{"name":"Tarui Seiichiro"},{"name":"Wada Hiroshi"}]},"publication_date":"1991","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.110","number":"No.1","starting_page":"9","ending_page":"11","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-924X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162456","label":"url"}],"paper_title":{"en":"Presynaptic localization of histamine H3-receptors in rat brain.","ja":"Presynaptic localization of histamine H3-receptors in rat brain."},"authors":{"en":[{"name":"Fujimoto Katsumi"},{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Wada Hiroshi"}],"ja":[{"name":"Fujimoto Katsumi"},{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"Wada Hiroshi"}]},"publication_date":"1991","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.177","number":"No.3","starting_page":"907","ending_page":"912","languages":["eng"],"referee":true,"identifiers":{"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162454","label":"url"}],"paper_title":{"en":"Synaptic and extra-synaptic distribution of histamine H1-receptors in rat and guinea pig brains.","ja":"Synaptic and extra-synaptic distribution of histamine H1-receptors in rat and guinea pig brains."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Fukui Hiroyuki"},{"name":"Yabumoto Masami"},{"name":"Wada Hiroshi"}],"ja":[{"name":"水口 博之"},{"name":"福井 裕行"},{"name":"Yabumoto Masami"},{"name":"Wada Hiroshi"}]},"publication_date":"1991","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.174","number":"No.2","starting_page":"1043","ending_page":"1047","languages":["eng"],"referee":true,"identifiers":{"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162453","label":"url"}],"paper_title":{"en":"Immuno-cross-reactivity of histidine and dopa decarboxylases.","ja":"Immuno-cross-reactivity of histidine and dopa decarboxylases."},"authors":{"en":[{"name":"Mizuguchi Hiroyuki"},{"name":"Yabumoto Masami"},{"name":"Imamura Ikuo"},{"name":"Fukui Hiroyuki"},{"name":"Wada Hiroshi"}],"ja":[{"name":"水口 博之"},{"name":"Yabumoto Masami"},{"name":"Imamura Ikuo"},{"name":"福井 裕行"},{"name":"Wada Hiroshi"}]},"publication_date":"1990","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.173","number":"No.3","starting_page":"1299","ending_page":"1303","languages":["eng"],"referee":true,"identifiers":{"issn":["0006-291X"]},"published_paper_type":"scientific_journal"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40017239607/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1522262179728141952/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=235114","label":"url"}],"paper_title":{"en":"ナノ粒子による炎症性伝達物質吸着を利用した炎症制御の研究","ja":"ナノ粒子による炎症性伝達物質吸着を利用した炎症制御の研究"},"authors":{"en":[{"name":"Mio Mitsunobu"},{"name":"Kogoma Masuhiro"},{"name":"Fukui Hiroyuki"},{"name":"Takeda Atsushi"}],"ja":[{"name":"見尾 光庸"},{"name":"小駒 益弘"},{"name":"福井 裕行"},{"name":"竹田 篤"}]},"publication_date":"2010-08","publication_name":{"en":"Chemical engineering","ja":"ケミカルエンジニヤリング"},"volume":"Vol.55","number":"No.8","starting_page":"603","ending_page":"608","languages":["jpn"],"identifiers":{"issn":["0387-1037"]},"published_paper_type":"research_institution"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.springerlink.com/link.asp?id=cxlt1ajm3cwmjlw3","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15054595","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=137841","label":"url"}],"paper_title":{"en":"Up-regulation of histamine H1 receptors in an allergic rat nasal mucosa model","ja":"Up-regulation of histamine H1 receptors in an allergic rat nasal mucosa model"},"authors":{"en":[{"name":"Murata Yuki"},{"name":"Miyoshi Ayako"},{"name":"Kitamura Yoshiaki"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"Murata Yuki"},{"name":"Miyoshi Ayako"},{"name":"北村 嘉章"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"publication_date":"2004-03-05","publication_name":{"en":"Inflammation Research","ja":"Inflammation Research"},"volume":"Vol.53","number":"No.Suppl 1","starting_page":"S11","ending_page":"S12","languages":["eng"],"identifiers":{"doi":["10.1007/s00011-003-0304-7"],"issn":["1023-3830"]},"published_paper_type":"research_institution"}}
{"insert":{"user_id":"1000029563","type":"published_papers"},"force":{"see_also":[{"@id":"http://www.springerlink.com/link.asp?id=v8lc4tybh19fkurb","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15054596","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=137839","label":"url"}],"paper_title":{"en":"Increase in the level of histidine decarboxylase mRNA expression in nasal mucosa of rats sensitized by toluene diisocyanate","ja":"Increase in the level of histidine decarboxylase mRNA expression in nasal mucosa of rats sensitized by toluene diisocyanate"},"authors":{"en":[{"name":"Kitamura Yoshiaki"},{"name":"Miyoshi Ayako"},{"name":"Maeyama K"},{"name":"Takeda Noriaki"},{"name":"Fukui Hiroyuki"}],"ja":[{"name":"北村 嘉章"},{"name":"Miyoshi Ayako"},{"name":"Maeyama K"},{"name":"武田 憲昭"},{"name":"福井 裕行"}]},"publication_date":"2004-03-05","publication_name":{"en":"Inflammation Research","ja":"Inflammation Research"},"volume":"Vol.53","number":"No.Suppl 1","starting_page":"S13","ending_page":"S14","languages":["eng"],"identifiers":{"doi":["10.1007/s00011-003-0305-6"],"issn":["1023-3830"]},"published_paper_type":"research_institution"}}