Shigemasa Tomioka, Miyuki Kaneko and Nobuyoshi Nakajo : Pentobarbital inhibits glucose uptake, but not water transport by glucose transporter type 3, NeuroReport, 23, 11, 687-691, 2012.
(要約)
To understand the mechanisms underlying the neuroprotective efficacy of barbiturates, the effect of pentobarbital on glucose uptake and water transport was determined in Xenopus oocytes expressing glucose transporter type 3 (GLUT3). Pentobarbital induced a 50% concentration-dependent inhibition in glucose uptake, but exerted no effect on water transport by GLUT3. Eadie-Hofstee analysis showed that pentobarbital decreased Vmax significantly, but not Km of GLUT3 for 2-deoxy-D-glucose. Although the protein kinase C (PKC) activator significantly decreased glucose uptake by GLUT3, no additive or synergistic interactions were observed between the PKC activator and pentobarbital. Our results suggest that pentobarbital may play an important role in neuroprotection by inhibition of glucose uptake by GLUT3 by a mechanism involving PKC.
(キーワード)
Animals / Biological Transport / GABA Modulators / Glucose / Glucose Transporter Type 3 / Neuroprotective Agents / Oocytes / Pentobarbital / Protein Kinase C / Water / Xenopus laevis
Shigemasa Tomioka and Nobuyoshi Nakajo : Beta-adrenergic blocker for hyperventilation syndrome in dentistry: A report of three cases, Oral Science International, 8, 1, 34-35, 2011.
Shigemasa Tomioka, Miyuki Kaneko, Kazuhito Satomura, Tomiko Mikyu and Nobuyoshi Nakajo : Effects of ketamine on glucose uptake by glucose transporter type 3 expressed in Xenopus oocytes: The role of protein kinase C, Biochemical and Biophysical Research Communications, 388, 1, 141-145, 2009.
(要約)
We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-d-[1,2-(3)H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10microM) significantly increased V(max) but not K(m) of GLUT3 for 2-deoxy-d-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucose uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.
(キーワード)
Animals / Biological Transport / Glucose / Glucose Transporter Type 3 / Ketamine / Oocytes / Protein Kinase C / Stereoisomerism / Xenopus laevis
Satoru Eguchi, Takashi Kawano, hua Yin, Katsuya Tanaka, Sonoko Yasui, Kazuaki Mawatari, Akira Takahashi, Yutaka Nakaya, Shuzo Oshita and Nobuyoshi Nakajo : Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels., Journal of Cardiovascular Pharmacology, 50, 6, 686-691, 2007.
(要約)
BACKGROUND: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited. METHODS: The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments.Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells. RESULTS: PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 microM). CONCLUSIONS: The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.
A 17-year-old man with fracture of the mandible underwent open fixation under general anesthesia. He was an athlete of the rugby suffering the fracture in a match. His preoperative physical examinations were normal except for I degrees atrioventricular block on electrocardiogram (ECG). During anesthesia, atrioventricular dissociation and frequent premature ventricular contractions were induced by the stimulation of nasotracheal intubation and the administration of atropine for the reversal of muscle relaxation. We thought the cause of the arrhythmia is the athlete's heart which may be vagotonic and may induce vagal reflex or fatal arrhythmia. This case demonstrates that it is necessary to pay attention to chronotropic action associated with the intubation of nasopharynx, the handling of laryngoscope and the usage of drugs for the anesthetic management of the athlete.
(キーワード)
スポーツ心臓 / 房室解離 / 変時作用
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15966390
Nicorandil, a hybrid ATP-sensitive potassium (K(ATP)) channel opener and nitrate compound, is used clinically for the treatment of angina pectoris. In the present study, we investigated the effects of propofol and thiamylal on sarcolemmal K(ATP) channels activities induced by nicorandil in cultured rat aortic smooth muscle cells. We used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on nicorandil induced K(ATP) channel activities. K(ATP) channel was not spontaneously activated by patch excision in the absence of intracellular ATP. Application of nicorandil (100 microM) induced a marked activation of KATP channel currents, which was completely blocked by 3 microM glibenclamide, the sulfonylurea that blocks K(ATP) channels. Nicorandil induced KATP channel currents were not significantly inhibited by application of 10 and 100 microM propofol to intracellular surface. However, application of 100 and 300 microM thiamylal to intracellular surface significantly inhibited the nicorandil induced K(ATP) channel currents, with relative channel activities decreasing to 0.65 +/- 0.08 and 0.46 +/- 0.10 of control, respectively. Propofol had no effect on nicorandil induced sarcolemmal KATP channel activities in rat aortic smooth muscle cells, whereas thiamylal significantly inhibited these channel activities at clinically relevant concentrations.
(キーワード)
ニコランジル / プロポフォール / チアミラール / Kチャネル / パッチクランプ法
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15852621
Naohiro Ohshita, Nobuyoshi Nakajo and Motohide Takemura : Characteristics of the trigeminal depressor response in cats, Journal of Japanese Dental Society of Anesthesiology, 33, 1, 111, 2005.
Naohiro Ohshita, Nobuyoshi Nakajo and Motohide Takemura : Characteristics of the trigeminal depressor response in cats, Journal of Neuroscience Research, 76, 6, 891-901, 2004.
(要約)
We studied the effects of electrical stimulation of the inferior alveolar nerve (IAN) on cardiovascular responses in cats. There was statistical correlation between cardiovascular response and prestimulus mean arterial blood pressure (MABP) and heart rate (HR). A trigeminal depressor response (TDR) was induced when the prestimulus MABP and HR were above 95 mm Hg and 140 beats/min, respectively. We investigated further to identify the vasomotor regulating center and neural transmitters involved in TDR. In the medulla, electrical stimulation of the dorsomedial medulla, the infratrigeminal nucleus (IFT), and the rostral ventrolateral medulla (RVLM) induced a vasopressor response. We confirmed that neurons in the RVLM were retrogradely labeled by wheat germ agglutinin-conjugated horseradish peroxidase injection into the nucleus intermediolateralis of the spinal cord. The vasopressor response induced by IFT stimulation was similar to that induced by IAN stimulation. Vasodepressor responses were induced when the caudal ventrolateral medulla, the nucleus tractus solitarius, the lateral tegmental field, the trigeminal nucleus interpolaris, the trigeminal spinal tract, and the paramedian reticular nucleus were stimulated. These responses, however, were not similar to the vasodepressor response induced by IAN stimulation but were similar to the cardiovascular response induced by vagal afferent stimulation. After spinalization or lesion of the RVLM, MABP and HR decreased and TDR completely disappeared. Inhibitory synaptic ligands and receptors were localized using immunohistochemical techniques. Neurons immunopositive for adrenaline, noradrenaline, and gamma-aminobutyric acid (GABA), and adrenaline alpha(2A), GABA(A), GABA(B), and glycine receptors were distributed along the sympatho-reflexive route including the RVLM and IFT. These results suggest that TDR could be induced as negative feedback to sympathetic hyperactivity whenever MABP and HR are high, because of the inhibitory control of the RVLM.
Satoru Eguchi, Kikuji Yamashita, Hiroyuki Morimoto, Tetsuo Ichikawa, Nobuyoshi Nakajo and Seiichiro Kitamura : Extracellular matrix formed by MC3T3-E1 osteoblast-like cells cultured on titanium 2. Collagen fiber formation, Connective Tissue, 36, 1, 9-15, 2004.
(要約)
Many aspects of the structures formed between titanium and cells and the mechanism of the formation are still unknown. In order to clarify these issues, we analyzed the initial structures formed between titanium and MC3T3-E1 osteoblast-like cells cultured on titanium. The present results indicate that extracellular matrix containing collagen fibers formed at the surface of a calcined layer on the titanium. At first, a hemispherical body and a small secondary spherical structure formed at the surface, followed by more beads to form a string-of-beads structure. These string-of-beads collagen structures elongated and formed spirals. For the first time ever, we directly observed the structure of collagen fiber formed between cultured osteoblasts and titanium with microscopy. Here, we describe the formation mechanism of type I collagen fibers in extracellular bone matrix. Elucidation of the mechanism of collagen fiber formation will aid in the development of controlled tissue regeneration.
Kikuji Yamashita, Satoru Eguchi, Hiroyuki Morimoto, Takeo Hanawa, Tetsuo Ichikawa, Nobuyoshi Nakajo and Seiichiro Kitamura : Extracellular matrix formed by MC3T3-E1 osteoblast-like cells cultured on titanium 1. Anchor structure, Connective Tissue, 36, 1, 1-8, 2004.
(要約)
In order to clarify the structure of the extracellular matrix formed by osteoblasts in contact with titanium, we analyzed the structure formed by cultured clonal MC3T3-E1 osteoblasts on a calcified surface of commercial pure titanium, after exfoliating the cells from the surface of the titanium. Collagen fibers formed between neighboring cells and between cells and titanium, in the latter case with one tip of each collagen fiber bound to the cell and the other tip bound to the surface of the titanium embedded in the calcified layer. We called this structure an "anchor structure", because the collagen fibers embedded in the calcified layer anchor the cells to the titanium. This structure may be a reason for the useful biocompatibility between titanium and bone.
(キーワード)
MC3T3-E1 / 細胞外マトリックス (extracellular matrix) / チタン (titanium) / type I collagen / anchor structure
Shigemasa Tomioka and Nobuyoshi Nakajo : No genotoxic effect of propofol in Chinese hamster ovary cells: Analysis by sister chromatid exchanges, Acta Anaesthesiologica Scandinavica, 44, 10, 1261-1265, 2001.
(要約)
In spite of its high placental transfer, propofol is frequently used in general anesthesia and sedation during obstetric and gynecological surgery such as in vitro fertilization. This study investigated whether or not propofol has a genotoxic potential by the sister chromatid exchange assay in vitro. Sister chromatid exchanges induced after exposure to propofol were measured in Chinese hamster ovary cells with and without metabolic activation. After propofol (0.2-20 microg ml(-1)) diluted dimethyl sulfoxide was applied for 2 h with or without S9 mix, the cells having been incubated for two metaphases (34 h) in the presence of 5'-bromo-2-deoxyuridine. N-nitrosodimethylamine and mitomycin C were used as positive controls with and without metabolic activation. The chromosomes were stained with the fluorescence plus Giemsa method, and then sister chromatid exchanges in 50 cells were counted for each concentration. Although increasing concentrations of propofol inhibited cell proliferation, no concentrations of propofol used in this study increased the sister chromatid exchange values, with and without metabolic activation. It was concluded that there was no indication, from the sister chromatid exchange assay in mammalian cells, of a genotoxic effect of propofol and its metabolites.
Shigemasa Tomioka, Tomiko Kurio, Kazumi Takaishi and Nobuyoshi Nakajo : Propofol Is Effective in Chemotherapy-Induced Nausea and Vomiting:A Case Report with Quantitative Analysis, Anesthesia & Analgesia, 89, 3, 798-799, 1999.
Shigemasa Tomioka, Nobuyoshi Nakajo and M Takata : INHIBITION OF STYLOGLOSSUS MOTONEURONS DURING THE PALATALLY INDUCED JAW-CLOSING REFLEX, Neuroscience, 92, 1, 353-360, 1999.
(要約)
The inhibition of hypoglossal motoneurons innervating the styloglossus muscle during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and inhibitory postsynaptic potentials in the styloglossus motoneurons, indicating that mechanosensory inputs from the posterior palatal mucosa sent inhibitory synaptic inputs to styloglossus motoneurons. We also demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In all of 22 styloglossus motoneurons studied, the depression of firing was elicited after the onset of jaw closure. In 14 of 22 styloglossus motoneurons, the depression of firing was elicited in the closing phase, and in the remaining cells it was elicited in the occlusal phase. By increasing the intracellular concentration of chloride ions, the inhibitory postsynaptic potential elicited in the styloglossus motoneuron converted to a depolarizing potential. It is concluded that the inhibition of styloglossus motoneurons may be involved in the maintenance of tongue protrusions during the palatally induced jaw-closing reflex, and that inhibitory postsynaptic potentials evoked in the styloglossus motoneurons are partly due to a chloride-dependent inhibitory postsynaptic potential.
Shigemasa Tomioka, Daisuke Uchida, Satoru Eguchi and Nobuyoshi Nakajo : Elimination of hypersensitive gagging reaction to dentistry by propofol at subhypnotic doses, Oral Diseases, 4, 4, 279-280, 1998.
(要約)
We describe a 44-year-old male patient with severe gagging reaction successfully treated without sedative effect by a continuous infusion of propofol. Propofol at subhypnotic doses seemed to be effective in eliminating hypersensitive gagging reaction to dentistry.
Shigemasa Tomioka, Nobuyoshi Nakajo and M Takata : Excitation of hypoglossal motoneurons responsible for tongue protrusions is associated with palatally induced jaw-closing reflex, Neuroscience, 78, 2, 603-612, 1997.
(要約)
The excitation of hypoglossal motoneurons innervating the genioglossus and geniohyoid muscles during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex, and it was found that mechanosensory inputs from the posterior palatal mucosa sent excitatory synaptic inputs to both genioglossus and geniohyoid motoneurons. We demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In five of 27 genioglossus motoneurons and nine of 23 geniohyoid motoneurons, the onset of burst was elicited before the onset of jaw closure. The remaining cells produced the onset of burst in the closing phase and in the initial part of the occlusal phase. However, the onset of excitatory postsynaptic potentials was 75-180 ms (n=20), earlier than that of jaw closure. During the jaw-closing reflex, the genioglossus and geniohyoid motoneurons were excited during the same phase of jaw movements and there was no difference in the onset of firing between the genioglossus and geniohyoid motoneurons. It is concluded that the excitation of the genioglossus and geniohyoid motoneurons may be associated with tongue protrusions during the palatally induced jaw-closing reflex.
Shigemasa Tomioka, Satoru Eguchi, Naoko Bando and Nobuyoshi Nakajo : Effects of Midazolam and Flumazenil on Reflex Potentials of the Hypoglossal Nerve Evoked by Stimulation of the Palate, Dentistry in Japan, 32, 116-119, 1995.
M Takata, Shigemasa Tomioka and Nobuyoshi Nakajo : Excitation and inhibition of trigeminal motoneurons by palatal stimulation, Experimental Brain Research, 87, 497-504, 1991.
M Takata, N Tomomune, T Nagahama, Shigemasa Tomioka and Nobuyoshi Nakajo : Synaptic efficacy of inhibitory synapses and repetitive firing in the reinnervating trigeminal and hypoglossal motoneurons, Neuroscience, 36, 3, 785-792, 1990.
Kazumi Takaishi, Shigemasa Tomioka and Nobuyoshi Nakajo : Effects of Local Anesthetics on Nitric Oxide Production in Cultured Bovine Aortic Endothlial Cells, 2001 ASA Annual Meeting, Oct. 2001.
Kazumi Takaishi, Shigemasa Tomioka and Nobuyoshi Nakajo : Effects of Local Anesthetics on L-arginine Transport in Cultured Bovine Aortic Endothlial Cells, 2000 ASA Annual Meeting, Oct. 2000.