Basic and applied studies on cardiotonic

近年来，有许多人致力于寻找和开发新的强心剂，这些强心剂比强心苷或儿茶酚胺更有效、更有选择性。[8]-姜辣素对豚鼠左心房有浓度依赖性正性变力作用。姜辣素的变力作用可被兰诺定消除。此外，我们的药理研究表明，增强肌浆网(SR)的钙泵活性在姜辣素的强心作用中起着重要作用。我们合成了姜酚相关化合物AP-004、AP-005和AP-015，并研究了这些化合物对SR的Ca~(2+)&lt；2+&gt；-ATPase活性的影响。这些化合物以浓度依赖的方式提高了Ca~(2+)&lt；2+&gt；-ATPase活性和Ca~(2+)&gt；-泵活性。在…中，姜酚类似物分子中的邻甲氧基苯酚和氢碳链可能都是激活钙泵ATPA的必要条件。在我们对具有独特作用机制的天然强心物质的研究过程中，从冲绳海绵Xestospongia Sapra中分离纯化了具有强烈强心作用的XQN。我们的药理学数据表明，细胞内cAMP含量的增加和跨细胞膜的Ca~(2+)~(2+)内流有助于XQN引起的强心反应的晚期，而早期阶段可能主要是通过直接激活收缩元件而引起的。心清宁可能为有价值的强心剂提供一种新的先导化合物。与N-乙基马来酰亚胺不同，用Xestoxinone修饰每个肌球蛋白2摩尔的SH基团可显著提高肌动球蛋白ATPase的活性。XQN通过修饰肌球蛋白中不同于SH_1和SH_2的特定SH基团，激活肌球蛋白ATPase。吴茱萸果实丙酮粗提物对豚鼠左心房有正性变力作用，其作用机制可能是一种新的机制。较少

During recent years there have been numerous effeors to find and develop novel cardiotonic agensts that are more effeorive and more selective than the cardiac glycosides or catecholamines. [8]-Gingerol produced a concentration-dependent positive inotropic effect on guinea pig isolated left atria. The inotropic effect of gingerol was abolished by ryanodine. Furthermore, our pharmacological studies suggest that the enhancement of the Ca^<2+>-pumping activity of sarcoplasmic reticulum (SR) plays an important role in the cardiotonic action of gingerol. We synthesized gingerol related compounds (AP-004, AP-005 and AP-015) and investigated the effects of these compounds on the Ca^<2+>-ATPase activity of SR.The Ca^<2+>-ATPase activity and the Ca^<2+>-pumping activity increased by these compounds in a concentration-dependent manner. It is probable that both o-methoxy phenol and hydeocarbon chain in the molecule of gingerol analogues are a request for activation of the Ca^<2+>-pumping ATPase.In … More the course of our survey of cardiotonic substances from natural sources having unique mechanism of action, xestoquinone (XQN) was isolated and purified as a powerfully cardiotonic principle of an Okinawa sea sponge Xestospongia sapra. Our pharmacological data suggest that an enhancement of intracellular cyclic AMP content and Ca^<2+> influx across the cell membrane contribute to the late phase of XQN-caused cardiotonic responses, wheres the early phase may largely be elicited through direct activation of contractile elements. XQN may provide an novel leading compound for valuable cardiotonic agents. Unlike N-ethylmaleimide, modification of 2 mol of SH groups per myosin by xestoxinone caused a marked increase in the actomyosin ATPase activity. XQN modifies the specific SH groups in myosin distinct from SH_1 and SH_2, resulting in activation of actocyosin ATPase.The crude acetone extract of the fruits of Evodia retaecarpa Bentham (Rutaceae) exhibited a positive inotropic effect with a novel mechanism on the guinea pig isolated left atria. Less