Journal of Pharmacological Sciences | |
Effects of Nicorandil on the cAMP-Dependent Cl− Current in Guinea-Pig Ventricular Cells | |
Hiroyuki Daida2  Kazumasa Suzuki1  Nami Nishimura1  Yoshie Reien1  Haruaki Nakaya1  Yuji Nakazato2  Yuuichi Miyata1  Akio Matsumoto1  Takehiko Ogura1  | |
[1] Department of Pharmacology, Chiba University Graduate School of Medicine, Japan;Department of Cardiology, Juntendo University School of Medicine, Japan | |
关键词: cAMP-dependent Cl− current; nicorandil; heart; nitric oxide (NO); cGMP; | |
DOI : 10.1254/jphs.09237FP | |
学科分类:药学 | |
来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society | |
【 摘 要 】
References(45)Cited-By(2)In guinea-pig cardiomyocytes, a cAMP-dependent Cl− current (ICl,cAMP) flows through a cardiac isoform of the cystic fibrosis transmembrane conductance regulator (CFTR), which belongs to a family of the ATP-binding cassette (ABC) proteins. Although several K+-channel openers and sulfonylurea ATP-sensitive K+ (KATP)–channel blockers reportedly inhibit ICl,cAMP, effects of nicorandil on the Cl− current have not been evaluated. This study was conducted to examine the effects of nicorandil on ICl,cAMP in isolated guinea-pig ventricular cells using patch clamp techniques. Nicorandil in concentrations higher than 300 μM enhanced the ICl,cAMP preactivated by 0.1 μM isoproterenol. The isoproterenol-induced ICl,cAMP was inhibited by 100 μM glibenclamide, but not by 100 μM pinacidil. SNAP (S-nitroso-N-acetyl-D,L-penicillamine, 10 μM), a nitric oxide (NO) donor, similarly enhanced the isoproterenol-induced ICl,cAMP. However, SG-86, a denitrated metabolite possessing K+ channel–opening action, failed to enhance the Cl− current. When the ICl,cAMP was activated by 3-isobutyl-1-methylxanthine (IBMX, 30 μM), either nicorandil or SNAP failed to enhance the isoproterenol-induced ICl,cAMP. Thus, nicorandil enhances ICl,cAMP in guinea-pig cardiomyocytes through an increase in intracellular cGMP, although direct modulation of ICl,cAMP by NO cannot be completely excluded.
【 授权许可】
Unknown
【 预 览 】
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