2011 Fiscal Year Final Research Report
Regulatory mechanisms and pathophysiological role of endothelin receptor-operated TRPC channels
| Project/Area Number |
21790236
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | エンドセリン受容体 / TRPCチャネル / 受容体作動性Ca^<2+>流入 / ストア作動性Ca^<2+>流入 / カルモジュリン / プロテインキナーゼA / リン酸化 |
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| Research Abstract |
The purpose of this study is to elucidate transient receptor potential canonical(TRPC) channels functioning as endothelin type A receptor(ET_AR)-operated Ca^<2+> channel and its regulatory mechanism. The results obtained from molecular pharmacological studies indicate that(1) both TRPC3 and TRPC6 contribute to ET_AR-operated Ca^<2+> entry,(2) G_<q/11> protein, phospholipase C, Src, phosphoinositide 3-kinase, calmodulin(CaM), and CaM/IP_3 receptor binding domain at the C terminus of TRPC3 and TRPC6 are involved in ET_AR-mediated Ca^<2+> entry via TRPC3 and TRPC6, and(3) TRPC6 is negatively regulated by protein kinase A-mediated phosphorylation of Ser^<28>
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[Journal Article] Adenylate cyclase/cAMP/protein kinase A signaling pathway inhibits endothelin type A receptor-operated Ca^<2+> entry mediated via transient receptor potential canonical 6 channels2012
Author(s)
Horinouchi, T., Higa, T., Aoyagi, H., Nishiya, T., Terada, K., Miwa, S.
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Journal Title
J. Pharmacol. Exp. Ther
Volume: 340
Pages: 143-151
Peer Reviewed
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[Journal Article] Function and regulation of endothelin type a receptor-operated transient receptor potential canonical channels2011
Author(s)
Horinouchi, T., Terada, K., Higa, T., Aoyagi, H., Nishiya, T., Suzuki, H., Miwa, S.
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Journal Title
J. Pharmacol. Sci.
Volume: 117
Pages: 295-306
Peer Reviewed
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[Journal Article] Endothelin type B receptor-induced sustained Ca^<2+> influx involves G_<q/11>/phospholipase C-independent, p38 mitogen-activated protein kinase-dependent activation of Na^+/H^+exchanger2010
Author(s)
Higa, T., Horinouchi, T., Aoyagi, H., Asano, H., Nishiya, T., Nishimoto, A., Muramatsu, I., Miwa, S.
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Journal Title
J. Pharmacol. Sci.
Volume: 113
Pages: 276-280
Peer Reviewed
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[Journal Article] Jab1 regulates levels of endothelin type A and B receptors by promoting ubiquitination and degradation2010
Author(s)
Nishimoto, A., Lu, L., Hayashi, M., Nishiya, T., Horinouchi, T., Miwa, S.
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Journal Title
Biochem Biophys Res Commun.
Volume: 391
Pages: 1616-1622
Peer Reviewed
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[Journal Article] Differential coupling of human endothelin type A receptor to G_<q/11> and_G<12> proteins : the functional significance of receptor expression level in generating multiple receptor signaling2009
Author(s)
Horinouchi, T., Asano, H., Higa, T., Nishimoto, A., Nishiya, T., Muramatsu, I., Miwa, S.
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Journal Title
J. Pharmacol. Sci.
Volume: 111
Pages: 338-351
Peer Reviewed
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