Takeya K, Itoigawa M, Furukawa H
Department of Pharmacology, Aichi Medical University, Japan.
Eur J Pharmacol. 1989 Oct 4;169(1):137-45. doi: 10.1016/0014-2999(89)90825-x.
Murrayaquinone-A, a carbazole alkaloid, was found to produce a triphasic inotropic response (first positive, second negative and third positive phases) of guinea-pig papillary muscle that normally paced at a slow rate of 0.2 Hz in Krebs-Henseleit solution at 30 degrees C. Murrayaquinone-A produced a concentration-dependent (10(-6) M-10(-4) M) positive inotropic effect (pD2 value 5.27 evaluated at the first phase). The triphasic pattern of inotropism of murrayaquinone-A was unaffected by reserpine, metoprolol or cimetidine treatment. Murrayaquinone-A increased the initial upstroke and the duration of the slow action potential in partially depolarized muscle (external K+ = 30 mEq). Murrayaquinone-A did not cause any positive inotropy under anoxic conditions and in the presence of 2,4-dinitrophenol and dicumarol. These results indicated that the triphasic inotropic effect of murrayaquinone-A is not mediated through a receptor mechanism but through a novel mechanism involving mitochondrial ATP production, thereby increasing the slow inward calcium current across the cardiac cell membrane via cyclic AMP converted from mitochondrial ATP.
九里香醌 - A，一种咔唑生物碱，发现在30摄氏度的Krebs - Henseleit溶液中，以0.2 Hz的缓慢速率正常起搏的豚鼠乳头肌产生三相变力反应（第一相为正，第二相为负，第三相为正）。九里香醌 - A产生浓度依赖性（10^(-6) M - 10^(-4) M）正性肌力作用（在第一相评估的pD2值为5.27）。利血平、美托洛尔或西咪替丁处理不影响九里香醌 - A的三相变力模式。九里香醌 - A增加部分去极化肌肉（细胞外K+ = 30 mEq）的初始上升速率和慢动作电位的持续时间。在缺氧条件下以及存在2,4 - 二硝基苯酚和双香豆素时，九里香醌 - A不会引起任何正性肌力作用。这些结果表明，九里香醌 - A的三相变力作用不是通过受体机制介导的，而是通过一种涉及线粒体ATP生成的新机制介导的，从而通过由线粒体ATP转化而来的环磷酸腺苷增加跨心肌细胞膜的慢内向钙电流。
