Kafiluddi R, Kennedy R H, Seifen E
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Eur J Pharmacol. 1989 Jun 20;165(2-3):181-9. doi: 10.1016/0014-2999(89)90711-5.
Experiments examined effects of extracellular Mg2+ concentration (Mgo2+) on dose-dependent actions of strophanthidin, norepinephrine, Bay K-8644 and extracellular Ca2+ (Cao2+) in electrically stimulated atrial and ventricular muscle isolated from guinea pig heart. Mgo2+ itself elicited a concentration-dependent negative inotropic effect. Elevation of Mgo2+ between 0.6 and 12 mM increased the concentration of strophanthidin necessary to produce its toxic effects without affecting the maximum developed tension prior to toxicity. Similarly, Mgo2+ did not alter the maximum contractile force elicited by cumulative addition of norepinephrine, Bay K-8644 or Cao2+, but increased their ED50 values. These data suggest that interactions between Mgo2+ and the four positive inotropic agents were not mediated by effects on receptor binding or Na+,K+-ATPase, but rather by alterations at one or more steps involved in excitation-contraction coupling.
实验研究了细胞外镁离子浓度(Mgo2+)对毒毛花苷、去甲肾上腺素、Bay K-8644以及细胞外钙离子(Cao2+)在豚鼠心脏分离的电刺激心房和心室肌中剂量依赖性作用的影响。Mgo2+自身可引发浓度依赖性负性肌力作用。在0.6至12 mM之间升高Mgo2+,会增加产生毒毛花苷毒性作用所需的浓度,而不影响毒性出现前的最大张力。同样,Mgo2+不会改变去甲肾上腺素、Bay K-8644或Cao2+累积添加所引发的最大收缩力,但会增加它们的半数有效剂量(ED50)值。这些数据表明,Mgo2+与这四种正性肌力药物之间的相互作用并非通过对受体结合或钠钾ATP酶的影响介导,而是通过兴奋 - 收缩偶联中一个或多个步骤的改变介导。