Tokushima University / Educator and Researcher Directory --- Inagaki, Akihiro

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Tokushima University ⟩ Graduate School of Biomedical Sciences ⟩ 医学域 ⟩ Medical Science ⟩ Physiological Sciences ⟩ Department of Integrative Physiology ⟩
Tokushima University ⟩ Faculty of Medicine ⟩ School of Medicine ⟩ Course of Integrated Brain Sciences ⟩ Integrative Physiology ⟩

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Research

Personal Web Page

https://researchmap.jp/read0065348 (researchmap)

Field of Study

○	Cell Physiology

Subject of Study

○	Ion transport (gastrointestinal tract) (Electrophysiology, Patch-clamp, Ussing chamber, Colon, Absorbtion and secretion)

Book / Paper

Academic Paper (Judged Full Paper):

1.	Akihiro Inagaki, Mikio Hayashi, Naaz Andharia and Hiroko Matsuda : Involvement of butyrate in electrogenic K+ secretion in rat rectal colon., Pflügers Archiv : European Journal of Physiology, Vol.471, No.2, 313-327, 2018. (Summary) Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are synthesized from dietary carbohydrates by colonic bacterial fermentation. These SCFAs supply energy, suppress cancer, and affect ion transport. However, their roles in ion transport and regulation in the intracellular environment remain unknown. In order to elucidate the roles of SCFAs, we measured short-circuit currents (ISC) and performed RT-PCR and immunohistochemical analyses of ion transporters in rat rectal colon. The application of 30 mM butyrate shifted ISC in a negative direction, but did not attenuate the activity of epithelial Na+ channels (ENaC). The application of bumetanide, a Na+-K+-2Cl- cotransporter inhibitor, to the basolateral side reduced the negative ISC shift induced by butyrate. The application of XE991, a KCNQ-type K+ channel inhibitor, to the apical side decreased the ISC shift induced by butyrate in a dose-dependent manner. The ISC shift was independent of HCO3- and insensitive to ibuprofen, an SMCT1 inhibitor. The mucosa from rat rectal colon expressed mRNAs of H+-coupled monocarboxylate transporters (MCT1, MCT4, and MCT5, also referred to as SLC16A1, SLC16A3, and SLC16A4, respectively). RT-PCR and immunofluorescence analyses demonstrated that KCNQ2 and KCNQ4 localized to the apical membrane of surface cells in rat rectal colon. These results indicate that butyrate, which may be transported by H+-coupled monocarboxylate transporters, activates K+ secretion through KCNQ-type K+ channels on the apical membrane in rat rectal colon. KCNQ-type K+ channels may play a role in intestinal secretion and defense mechanisms in the gastrointestinal tract. (Keyword) KCNQ / Rectal colon / Short-chain fatty acid / Short-circuit current (Tokushima University Institutional Repository) ● Metadata: 115682 (Link to Publication Site) ● Publication site (DOI): 10.1007/s00424-018-2208-y (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30250967 ● Search Scopus @ Elsevier (PMID): 30250967 ● Search Scopus @ Elsevier (DOI): 10.1007/s00424-018-2208-y (Tokushima University Institutional Repository: 115682, DOI: 10.1007/s00424-018-2208-y, PubMed: 30250967)
2.	Mikio Hayashi, Akihiro Inagaki, Novak Ivana and Hiroko Matsuda : The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells., Pflügers Archiv : European Journal of Physiology, Vol.468, No.7, 1171-1181, 2016. (Summary) Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl(-) channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (V te) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 M, which corresponded to the value obtained on whole-cell Cl(-) currents in Capan-1 single cells. The effects of adenosine on V te, an equivalent short-circuit current (I sc), and whole-cell Cl(-) currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased I sc and whole-cell Cl(-) currents through CFTR Cl(-) channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of I sc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl(-) currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl(-) channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion. (Keyword) adenosine receptor / CFTR / Cl channel / Duct / Pancreas (Tokushima University Institutional Repository) ● Metadata: 115683 (Link to Publication Site) ● Publication site (DOI): 10.1007/s00424-016-1806-9 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26965147 ● Search Scopus @ Elsevier (PMID): 26965147 ● Search Scopus @ Elsevier (DOI): 10.1007/s00424-016-1806-9 (Tokushima University Institutional Repository: 115683, DOI: 10.1007/s00424-016-1806-9, PubMed: 26965147)
3.	Akihiro Inagaki, Soichiro Yamaguchi, Hiromi Takahashi-Iwanaga, Toshihiko Iwanaga and Toru Ishikawa : Functional characterization of a ClC-2-like Cl(-) conductance in surface epithelial cells of rat rectal colon., The Journal of Membrane Biology, Vol.235, No.1, 27-41, 2010. (Summary) ClC-2, a member of the voltage-gated Cl(-) channel family, is expressed in the distal colonic surface epithelial cells of various species, but its functional significance remains unclear. Here, by means of electrophysiological and molecular biological techniques, we have identified and characterized a ClC-2-like conductance naturally expressed by surface epithelial cells acutely dissociated from rectal colon of rats fed a standard diet. Whole-cell patch-clamp experiments showed that the surface cells, whether an amiloride-sensitive Na(+) conductance was present or not, displayed a strong hyperpolarization-activated, inwardly rectifying Cl(-) current. Analysis both by in situ hybridization and immunohistochemistry confirmed the expression of ClC-2 in the rectal surface epithelium. The native Cl(-) current shared common electrophysiological properties including voltage-dependent activation, anion selectivity sequence, and Zn(2+) sensitivity with that recorded from HEK293 cells transfected with ClC-2 cloned from rat rectal colon (rClC-2). Cell-attached patch recordings on the surface cells revealed that native ClC-2-like currents activated only at potentials at least 40 mV more negative than resting membrane potentials. In Ussing chamber experiments with rat rectal mucosa, either basolateral or apical application of Zn(2+) (0.1 mM), which inhibited both native ClC-2-like currents and recombinant rClC-2 currents, had little, if any, effects on basal amiloride-sensitive short-circuit current. Collectively, these results not only demonstrate that a functional ClC-2-type Cl(-) channel is expressed in rat rectal surface epithelium, but also suggest that the channel activity may be negligible and thus nonessential for controlling electrogenic Na(+) transport in this surface epithelium under basal physiological conditions. (Link to Publication Site) ● Publication site (DOI): 10.1007/s00232-010-9253-6 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20411246 ● Search Scopus @ Elsevier (PMID): 20411246 ● Search Scopus @ Elsevier (DOI): 10.1007/s00232-010-9253-6 (DOI: 10.1007/s00232-010-9253-6, PubMed: 20411246)
4.	Akihiro Inagaki, Souichirou Yamaguchi and Toru Ishikawa : Amiloride-sensitive epithelial Na+ channel currents in surface cells of rat rectal colon., American Journal of Physiology, Cell Physiology, Vol.286, No.2, 380-390, 2004. (Summary) Surface cells of the mammalian distal colon are shown to molecularly express the amiloride-sensitive epithelial Na+ channel composed of three homologous subunits (alpha-, beta-, and gamma-ENaC). However, because basic electrophysiological properties of amiloride-sensitive Na+ channels expressed in these cells are largely unknown at the cellular level, functional evidence for the involvement of the subunits in the native channels is incomplete. Using electrophysiological techniques, we have now characterized functional properties of native ENaC in surface cells of rectal colon (RC) of rats fed a normal Na+ diet. Ussing chamber experiments showed that apical amiloride inhibited a basal short-circuit current in mucosal preparation of RC with an apparent half-inhibition constant (Ki) value of 0.20 microM. RT-PCR analysis confirmed the presence of transcripts of alpha-, beta-, and gamma-rENaC in rectal mucosa. Whole cell patch-clamp experiments in surface cells of intact crypts acutely isolated from rectal mucosa identified an inward cationic current, which was inhibited by amiloride with a Ki value of 0.12 microM at a membrane potential of -64 mV, the inhibition being weakly voltage dependent. Conductance ratios of the currents were Li+ (1.8) > Na+ (1) > K+ ( approximately 0), respectively. Amiloride-sensitive current amplitude was almost the same at 15 or 150 mM extracellular Na+, suggesting a high Na+ affinity for current activation. These results are consistent with the hypothesis that a heterooligomer composed of alpha-, beta-, and gamma-ENaC may be the molecular basis of the native channels, which are responsible for amiloride-sensitive electrogenic Na+ absorption in rat rectal colon. (Keyword) distal colon / electrogenic Na+ absorption / short-circuit current / whole cell patch clamp / alpha-beta-gamma-ENaC (Link to Publication Site) ● Publication site (DOI): 10.1152/ajpcell.00373.2003 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14576089 ● Search Scopus @ Elsevier (PMID): 14576089 ● Search Scopus @ Elsevier (DOI): 10.1152/ajpcell.00373.2003 (DOI: 10.1152/ajpcell.00373.2003, PubMed: 14576089)

Proceeding of Domestic Conference:

1.	Akihiro Inagaki, Mikio HAYASHI, Naaz ANDHARIA and Hiroko MATSUDA : Electrogenic K+ secretion induced by butyrate in rat rectal colon, The 96th Annual Meeting of the Physiological Society of Japan, Mar. 2019. (Keyword) large intestine / short-circuit current / potassium channel
2.	Mikio Hayashi, Akihiro Inagaki and Hiroko Matsuda : Functional expression of adenosine A2B receptor in pancreatic duct cells, The 94th Annual Meeting of the Physiological Society of Japan, Mar. 2017. (Keyword) Adenosine, Cl current, Epithelial transport, Duct, Pancreas
3.	Akihiro Inagaki, Mikio HAYASHI, Naaz ANDHARIA and Hiroko MATSUDA : Butyrate activates XE991 sensitive potassium secretion in rat rectal colon, The 94th Annual Meeting of the Physiological Society of Japan, Mar. 2017. (Keyword) large intestine, short-circuit current, potassium channel
4.	Akihiro Inagaki : Butyrate activates barium-resistant potassium secretion in a dose-dependent manner in rat rectal colon, The 93th Annual Meeting of the Physiological Society of Japan, Mar. 2016. (Keyword) large intestine, short-circuit current, potassium channel
5.	Akihiro Inagaki : ラット大腸において短鎖脂肪酸は定常性起電性K+分泌を活性化する, 第158回日本獣医学会学術集会, Sep. 2015. (Keyword) rat, colon, short-chain fatty acid, short-circuit current, K+ secretion
6.	Akihiro Inagaki : Short-chain fatty acid activates bicarbonate absorption or proton secretion in rat rectal colon, The 92th Annual Meeting of the Physiological Society of Japan, Mar. 2015. (Keyword) rat, colon, short-circuit current, intracellular pH regulation
7.	Akihiro Inagaki : Short-chain fatty acid activates electrogenic K+ secretion in rat colon, Hindgut Club Japan 2014, Dec. 2014.
8.	多田亜梨沙, Masatake Akutagawa, Takahiro Emoto, Shigeru Obara, Kazuo Yoshizaki, Akihiro Inagaki, Kazuyoshi Kitaoka, Hiroyuki Tanaka, Shinsuke Konaka and Yohsuke Kinouchi : 超音波ドプラ法を用いた血流速度測定装置のディジタル化に関する検討, Journal of Shikoku-Section Joint Convention of the Institutes of Electrical and Related Engineers, No.14-13, 241, Sep. 2014. (Summary) 頸動脈血流速度波形を測定することによって動脈硬化の程度など循環器系の様々な状態を知ることができることがわかってきた．小型血流速度測定装置が普及すると日常的に循環器の状態を測定することができるようになり，健康長寿社会へも繋げることもできるかもしれない．そのためには低雑音で扱いの容易な測定装置の開発が必須である．本研究ではFPGAなどのディジタル回路を用いて回路の主要部分再設計し，低雑音の測定装置の開発を試みた．
9.	Mikio Hayashi, Akihiro Inagaki and Hiroko Matsuda : Adenosine A2B receptor regulates CFTR in pancreatic duct cells, The 91th Annual Meeting of the Physiological Society of Japan, Mar. 2014. (Keyword) Adenosine receptor, Cystic fibrosis transmembrane conductance regulator, Epithelial transport, Duct, Pancreas
10.	Rentarou Inoue and Akihiro Inagaki : Short-chain fatty acid inhibits cAMP-activated short-circuit current in rat distal colon, The 91th Annual Meeting of the Physiological Society of Japan, Mar. 2014. (Keyword) Ussing-chamber, Cl secretion, GPR43
11.	Akihiro Inagaki : Short-chain fatty acid might increase intracellular Ca2+ concentration in rat colonic surface and crypt cells, The 91th Annual Meeting of the Physiological Society of Japan, Mar. 2014. (Keyword) rat, colon, SCFA, Fura-2, MCT1
12.	Akihiro Inagaki and Rentarou Inoue : SCFAs inhibit cAMP-activated short-circuit current in rat distal colon, Hindgut Club Japan 2013, Dec. 2013.
13.	Akihiro Inagaki, Mikio Hayashi and Hiroko Matsuda : Adenosine receptors regulate Cl- channels in pancreatic duct cells, The 90th Annual Meeting of the Physiological Society of Japan, Mar. 2013. (Keyword) Adenosine receptor, Epithelial transport, Duct, Pancreas
14.	Akihiro Inagaki : Butyrate-induced transient calcium elevation in rat distal colon, Hindgut Club Japan 2012, Dec. 2012. (Keyword) epithelial transport, rat colon, short-circuit-current, short-chain fatty acid
15.	Akihiro Inagaki : Segmentary difference of butyrate-induced transient current in rat distal colon, Hindgut Club Japan 2011, Dec. 2011. (Keyword) epithelial transport, rat colon, short-circuit-current, short-chain fatty acid
16.	Koki Aoyama, Shigeru Obara, Hiroyuki Tanaka, Kazuyoshi Kitaoka, Yuji Hirao, Masatake Akutagawa, Takahiro Emoto, Akihiro Inagaki, Shinsuke Konaka, Kazuo Yoshizaki and Yohsuke Kinouchi : 頚動脈血流速度パターンの折れ線近似を用いた評価, 第33回日本生体医工学会中国四国支部大会, 22, Sep. 2010.
17.	Akihiro Inagaki : The effects of butyrate on Na⁺-absorption and Cl^--secretion in rat rectal colon, The 87th Annual Meeting of the Physiological Society of Japan, May 2010. (Keyword) epithelial transport, rat colon, short-circuit-current, short-chain fatty acid
18.	Kazuyoshi Kitaoka, Hajime Miura, Mitsuo Kitamura, Akihiro Inagaki, Masatake Akutagawa, Yohsuke Kinouchi and Kazuo Yoshizaki : 起立動作時における予測的な脳血流量，総頸動脈血流速度の変化, Journal of Physiological Society of Japan, Vol.72, No.4, 126-127, 2010.
19.	神高宏明, Toshitaka Ikehara, Hisao Yamaguchi, Akihiro Inagaki, Kazuo Yoshizaki and Yohsuke Kinouchi : Effects of a Time-Varying Magnetic Field on Transient Increase in Intracellular Ca²⁺ in Cultured Chromaffin Cells, Journal of Shikoku-Section Joint Convention of the Institutes of Electrical and Related Engineers, 223, Sep. 2007.

Et cetera, Workshop:

1.	Mitsuo Kitamura, Akihiro Inagaki and Kazuo Yoshizaki : 生体試料測定のためのNMR装置特性の基礎的検討, Shikoku Acta Medica, Vol.61, No.1,2, 60, Apr. 2005.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

腎臓カリウム分泌機構における硫化水素を介したBKチャネルとHCNチャネルの機能連関 (Project/Area Number: 24K11433 )
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