Effect of amrinone on sodium-calcium exchange in cardiac sarcolemmal vesicles.
The mechanism of action of amrinone, a synthetic cardiotonic drug, is unknown. It has been postulated that it increases cardiac contractility by increasing intracellular free Ca++ concentration, in some manner. Purified cardiac sarcolemmal vesicles have been shown capable of carrying out Ca++ transport in either direction by Na+/Ca++ exchange. We have observed that amrinone inhibits Ca++ uptake by Na+/Ca++ exchange in such vesicles prepared from both guinea pig and rat hearts. The inhibitory effect is dose-dependent and maximal at a concentration of about 300 micrograms/ml. If amrinone decreases the rate of Ca++ efflux from myocardial cells in vivo during diastole by this mechanism, this action may account, at least in part, for the observed positive inotropic effect of the drug.
D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013045:Species Specificity
D000631:Aminopyridines; D002132:Calcium Radioisotopes; D002316:Cardiotonic Agents; D009124:Muscle Proteins; D012964:Sodium; D000676:Amrinone; D002118:Calcium