Mechanism of action of epinephrine and glucagon on the canine heart. Evidence for increase in sarcotubular calcium stores mediated by cyclic 3',5'-AMP.

Abstract

The mechanisms by which the catecholamines and glucagon increase myocardial contractility were investigated by studying the effects of cyclic 3', 5'-AMP, epinephrine, and glucagon on calcium accumulation by a microsomal fraction of canine myocardium thought to represent sarcoplasmic reticulum, and by assaying the microsomal fraction for adenyl cyclase activity. Each agent produced a concentration-dependent increase in calcium accumulation. Moreover, adenyl cyclase, an enzyme activated by epinephrine and glucagon and responsible for the production of cyclic 3', 5'-AMP, was present in the microsomal fraction. Its specific activity and responsiveness to epinephrine and glucagon were similar to that previously found in sarcolemmic fractions. The beta-receptor blocking agent propranolol abolished the activation of adenyl cyclase and increase in microsomal calcium accumulation produced by epinephrine, but was without effect when these same changes were produced by glucagon. These findings are consistent with the hypotheses that: (1) the positive inotropic effects of epinephrine and glucagon may occur as a result of an augmentation of the sarcotubular calcium pool(s); and (2) this effect is mediated, at least in part, by an elevation of cyclic 3', 5'-AMP levels produced by activation of an adenyl cyclase localized to the sarcoplasmic reticulum.