Hattori Y, Nakaya H, Tohse N, Kanno M
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Mar;337(3):323-30. doi: 10.1007/BF00168846.
Effects of organic Ca2+ channel antagonists, Ni2+ and ryanodine on the electrophysiological and positive inotropic responses to histamine were examined in isolated guinea-pig left atria. Histamine increased force of contraction, prolonged action potential duration (APD) and hyperpolarized the membrane in a concentration-dependent manner. Histamine at a concentration of 1 mumol/l produced a dual-component positive inotropic response composed of an initial increasing phase (initial component) and a second and late developing, greater positive inotropic phase (second component), whereas causing monophasic changes in APD and resting potential. The electrophysiological and dual-component positive inotropic effects induced by histamine were antagonized by chlorpheniramine (1 mumol/l) but not by cimetidine (10 mumol/l), indicating that both effects are exclusively mediated by H1-receptors. The positive inotropic response to 1 mumol/l histamine was changed by the pretreatment with nifedipine (1 mumol/l) and nisoldipine (1 mumol/l). In the presence of these dihydropyridines, the second component was almost completely abolished, while the initial component was hardly affected. On the other hand, verapamil (3 mumol/l) and diltiazem (10 mumol/l) failed to modify the multiphasic inotropic response to histamine. None of the Ca2+ channel antagonists affected the histamine-induced APD prolongation. In the presence of Ni2+ at a concentration of 0.3 mmol/l, at which it produced no negative inotropic action, the second component of the positive inotropic effect of histamine was specifically suppressed whereas the histamine-induced APD prolongation was unaffected. Preferential attenuation of the second component was also observed in the presence of 30 nmol/l ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
在离体豚鼠左心房中，研究了有机钙通道拮抗剂、镍离子（Ni2+）和兰尼碱对组胺电生理及正性肌力反应的影响。组胺以浓度依赖性方式增强收缩力、延长动作电位时程（APD）并使膜超极化。1μmol/L的组胺产生双相正性肌力反应，由初始增强相（初始成分）和第二个后期发展的、更大的正性肌力相（第二成分）组成，而对APD和静息电位产生单相变化。组胺诱导的电生理和双相正性肌力作用被氯苯那敏（1μmol/L）拮抗，但不被西咪替丁（10μmol/L）拮抗，表明这两种作用均仅由H1受体介导。用硝苯地平（1μmol/L）和尼索地平（1μmol/L）预处理可改变对1μmol/L组胺的正性肌力反应。在这些二氢吡啶存在下，第二成分几乎完全消失，而初始成分几乎不受影响。另一方面，维拉帕米（3μmol/L）和地尔硫䓬（10μmol/L）未能改变对组胺的多相正性肌力反应。钙通道拮抗剂均未影响组胺诱导的APD延长。在浓度为0.3mmol/L的Ni2+存在下，其不产生负性肌力作用，组胺正性肌力作用的第二成分被特异性抑制，而组胺诱导的APD延长不受影响。在30nmol/L兰尼碱存在下也观察到第二成分的优先减弱。（摘要截短至250字）
