Satoh E, Yanagisawa T, Taira N
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Jpn J Pharmacol. 1990 Oct;54(2):133-41. doi: 10.1254/jjp.54.133.
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 pA2 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.
在犬心房肌中研究了钾通道阻滞剂格列本脲对钾通道开放剂色满卡林、吡那地尔和尼可地尔负性肌力作用的拮抗方式。格列本脲使色满卡林、吡那地尔和尼可地尔的浓度-负性肌力作用曲线右移，而不影响基础收缩力。Schild分析得出格列本脲对三种钾通道开放剂的pA2值均一，为6.06 - 6.35。预先被色满卡林降低的心房肌收缩力也会随着格列本脲浓度的增加而被拮抗。格列本脲既不影响毒蕈碱受体偶联钾通道开放剂卡巴胆碱的浓度-负性肌力作用曲线，也不影响钙通道阻滞剂硝苯地平的该曲线。从这些结果可以明显看出，格列本脲在心脏变力性方面表现为色满卡林、吡那地尔和尼可地尔的药理学拮抗剂。这种拮抗作用似乎涉及格列本脲与这些钾通道开放剂的竞争，可能是在犬右心房肌的ATP敏感性通道处。
