MaxiK Channel Mediates β_2-Adrenoceptor-activated Relaxation to Isoprenaline through cAMP-dependent and -independent Mechanisms in Guinea-pig Tracheal Smooth Muscle
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概要
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We examined the contribution of large-conductance, Ca^<2+>-sensitive K^+ (MaxiK) channel to β_2-adrenoceptor-activated relaxation to isoprenaline in guinea-pig tracheal smooth muscle focusing on the role for cAMP in the coupling between β_2-adrenoceptor and MaxiK channel. Isoprenaline-elicited relaxation was confirmed to be mediated through β_2-type of adrenoceptor since the response was antagonized in a competitive fashion by a β_2-selective adrenoceptor antagonist butoxamine with a pA_2 value of 6.56. Isoprenaline-induced relaxation was significantly potentiated by a selective inhibitor of cyclic AMP-specific phosphodiesterase, Ro-20-1724 (0.1-1 μM). cAMP-dependent mediation of MaxiK channel in the relaxant response to isoprenaline was evidenced since the potentiated response to isoprenaline by the presence of Ro-20-1724 (1 μM) was inhibited by the channel selective blocker, iberiotoxin (IbTx, 100 nM). This concept was supported by the finding that the relaxation to a membrane permeable cAMP analogue, 8-bromo-cAMP (1 μM), was susceptible to the inhibition by IbTx. On the other hand, isoprenaline-induced relaxation was not practically diminished by an adenylyl cyclase inhibitor SQ 22,536 (100 μM). However, isoprenaline-induced relaxation in the presence of SQ 22,536 was suppressed by IbTx. Characteristics of isoprenaline-induced relaxant response, i.e., impervious to SQ 22,536 but susceptible to IbTx, were practically mimicked by cholera toxin (CTX, 5μg/ml), an activator of adenylyl cyclase coupled-heterotrimeric guanine nucleotide-binding regulatory protein G_s. These findings indicate that in guinea-pig tracheal smooth muscle: 1) MaxiK channel substantially mediates β_2-adrenoceptor-activated relaxation; 2) both cAMP-dependent and - independent mechanisms underlie the functional coupling between β_2-adrenoceptor and MaxiK channel to induce muscle relaxation; and 3) direct regulation of MaxiK channel by G_s operates in cAMP-independent coupling between β_2-adrenoceptor and this ion channel.
- 日本平滑筋学会の論文
著者
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KOIKE Katsuo
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
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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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Shigenobu K
Department Of Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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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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Tanaka Yoshio
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University
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Shigenobu Koki
Toho University School 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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Yamaki Fumiko
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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YAMASHITA Yoko
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
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Yamashita Yoko
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
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Yamashita Yoko
Department Of Biotechnology Kyoto Sangyo University
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Tanaka Yoshio
Department Of Chemical Pharmacology Toho University Faculty Of Pharmaceutical Sciences
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Tanaka Yoshio
Department Of Pharmacology Toho University Faculty 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 Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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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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