Specific antagonism by glibenclamide of negative inotropic effects of potassium channel openers in canine atrial muscle.
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概要
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The mode of antagonism by glibenclamide, a potassium channel blocker, of the negative inotropic effects of potassium channel openers, cromakalim, pinacidil and nicorandil, was investigated in canine atrial muscle. Glibenclamide shifted the concentration-negative inotropic effect curves for cromakalim, pinacidil and nicorandil to the right without affecting the basal force of contraction. Schild analysis yielded uniform pA<SUB>2</SUB> values of 6.06-6.35 for glibenclamide against the three potassium channel openers. The force of contraction of atrial muscles previously reduced by cromakalim was also antagonized by increasing concentrations of glibenclamide. Glibenclamide affected neither the concentration-negative inotropic effect curves for carbachol, an opener of the muscarinic receptor-coupled potassium channel, nor those for nifedipine, a calcium channel blocker. From these results, it became evident that glibenclamide behaved as a pharmacological antagonist of cromakalim, pinacidil and nicorandil in cardiac inotropy. The antagonism seems to involve competition of glibenclamide and these potassium channel openers, presumably at the ATP-sensitive channel in canine right atrial muscles.
- 公益社団法人 日本薬理学会の論文
著者
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Yanagisawa Teruyuki
Department Of Molecular Pharmacology Tohoku University Graduate School Of Medicine
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Satoh Eisaku
Department Of Pharmacology Akita University School Of Medicine
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TAIRA Norio
Department o f Pharmacology, Tohoku University, School of Medicine
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SATOH Eisaku
Department of Pharmacology, Tohoku University School of Medicine
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