Influence of highly unsaturated phosphatidylcholine on the effects of ouabain and some cardioactive drugs on cardiac contractile force and NA +,K +-ATPase activity

Abstract

Isolated left guinea pig auricles and cardiac Na,K-ATPase from calf heart were incubated with highly unsaturated phosphatidylcholine (PC) for 2 hr. Thereafter the actions of ouabain on Na, K-ATPase, and of ouabain, digoxin, digitoxin, isoproterenol, acetylcholine, pentobarbital and different extracellular Ca 2+ concentrations on contractile force of the auricles were investigated. PC itself altered neither the ATPase activity nor the intracellular ionic homeostasis, nor contractile force of the auricles. Similarly, the staircase phenomenon, the contractile response to different extracellular Ca 2+ concentrations, to pentobarbital and ouabain, and the extent of ouabain-induced inhibition of the ATPase were not influenced. In addition the toxicity of ouabain was not altered. However, the rate of development of the ouabain-induced ATPase inhibition, as well as of the positive inotropism and toxic effects of ouabain, digoxin and digitoxin was markedly reduced. The maximum inotropic effect of digoxin and digitoxin, and the toxicity of digitoxin were significantly enhanced. Remarkably, the binding of [ 3H]digitoxin was significantly diminished in PC-pre-incubated auricles, binding of [ 3H]ouabain, however, remained unchanged. The dose-response curves to isoproterenol and acetylcholine, the latter also in the presence of physostigmine, were markedly parallel-shifted to the right. The modifying effect of highly unsaturated PC on the action of the drugs studied is suggested to be due to an altered physico-chemical state (fluidity) of the outer surface of the cellular membrane.