Functional Contribution of Voltage-Dependent and Ca^2+-Activated K^+ (BK_ca) Channels to the Relaxation of Guinea-Pig Aorta in Response to Natriuretic Peptides
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概要
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We examined the relaxant effects of natriuretic peptide family on the isolated guinea-pig aorta to determine the receptor subtype which primarily mediates this vascular relaxation, with particular attention to the apparent contribution of voltage-dependent and Ca^2+-activated K^+ (BK_Ca) channels to the response. Three endogenous natriuretic peptide ligands (natriuretic peptide, ANP; brain natriuretic peptide, BNP; C-type natriuretic peptide, CNP) produced a concentration-dependent relaxation in de-endothelialized guinea-pig aorta pre-contracted by noradrenaline (NA), with a potency order of ANP≥BNP>>CNP. Although the relaxations elicited by these three natriuretic peptide ligands were significantly diminished by iberiotoxin (IbTx, 10^-7M), a selective BK_Ca channel blocker, the inhibitory effect of IbTx was most pronounced for the CNP-induced relaxation; when estimated at 10^-7 M of each peptide, the apparent extent of BK_Ca channel contribution to the total relaxant response was≈60% for CNP>≈20% for either ANP or BNP. Supporting the substantial role of BK_Ca channels in the vascular responses, high-KCl (80 mM) potently suppressed the relaxations induced by these natriuretic peptide ligands. The relaxant response to 8-Bromo-cyclic GMP, a membrane permeable cyclic GMP analogue, was also diminished by IbTx (10^-7 M) and high-KCl (80 mM), which indicates the key role of cyclic GMP in the BK_Ca channel-mediated, natriuretic peptide-elicited vascular relaxation. These results indicate that the A-type receptor (NPR-A, which is more selective for ANP and BNP) rather than the B-type receptor (NPR-B, which is more selective for CNP) predominates in the guinea-pig aorta as the natriuretic peptide receptor which mediates this vascular smooth muscle relaxation. Although activation of BK_Ca channels substantially contributes to both NPR-A- and NPR-B-activated relaxations, particularly in the NPR-B-activated relaxation, this K^+ channel may function as a primary relaxant mediator in this conduit artery.
著者
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KOIKE Katsuo
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
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TANAKA Hikaru
Department of Pharmacology, Toho University School of
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SHIGENOBU Koki
Department of Pharmacology, Toho University School of
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Koike Katsuo
東京薬科大学 内分泌分子薬理学
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Koike K
Toho Univ. School Of Pharmaceutical Sci. Chiba Jpn
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Koike Katsuo
Department Of Chemical Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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Tanaka Hikaru
Dep. Of Pharmacology Toho Univ. Fac. Of Pharmaceutical Sciences Jpn
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Shigenobu K
Department Of Pharmacology Toho University School Of Pharmaceutical Sciences
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Shigenobu Koki
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Tsuneoka Yayoi
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University
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Tanaka Yoshio
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University
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Tanaka Hikaru
Department Of Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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KOIKE Katsuo
Toho University School of Pharmaceutical Sciences
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Koike K
Toho Univ. Chiba Jpn
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Tanaka Yoshio
Dep. Of Chemical Pharmacology Fac. Of Pharmaceutical Sciences Toho Univ.
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Toyoda Yoshihiro
Sagami Research Laboratory Wakamoto Pharmaceutical Co. Ltd.
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Horinouchi Takahiro
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
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Horinouchi T
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
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Tanaka Yoshio
Department Of Chemical Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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OTSUKA Kazuoki
Department of Pharmacology, Toho University School of Pharmaceutical Sciences
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Tanaka Yoshio
Department Of Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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Tanaka Hikaru
Department Of Internal Medicine Sasebo Senjyu Hospital
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Otsuka Kazuoki
Department Of Pharmacology Toho University School Of Pharmaceutical Sciences
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Horinouchi Takahiro
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Tanaka Yoshio
Department Of Applied Chemistry Faculty Of Engineering Yokohama National University
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Horinouchi Takahiro
Department Of Cellular Pharmacology Graduate School Of Medicine Hokkaido University
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Tanaka Hikaru
Department Of Internal Medicine Hirosaki Municipal Hospital
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Tanaka Hikaru
Department of Endocrinology and Metabolism, Hirosaki University
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