Irrespective of the type and nature of stressful stimulus, elevated levels of circulating catecholamines are commonly observed. A small amount of catecholamines released in acute and mild stress is considered to increase heart function beneficially by binding to the β-adrenergic receptors, activating the adenylate cyclase system and raising the intracellular concentration of calcium (1,2). In this regard it should be mentioned that β-adrenergic receptors are coupled to adenylate cyclase by guanine nucleotide binding protein, and their activation by catecholamines is associated with formation of cyclic AMP, phosphorylation of Ca2+-channels through protein kinase and subsequent increase in the entry of Ca2+ into the myocardial cell. On the other hand, an excessive amount of catecholamine released in chronic and severe stress is believed to produce cardiotoxic effects which are associated with the occurrence of an intracellular Ca2+ overload and abnormalities in the excitation-contraction coupling process (3,4,5). Although participation of the β-adrenergic receptor-adenylate cyclase mechanism in raising the intracellular concentration of calcium is obvious at initial stages, its role in later stages with prolonged exposure of the myocardium to high doses of catecholamines is not clear at present. This view is based on the fact that prolonged exposure of tissue to catecholamines has been shown to produce desensitization of adrenergic receptors (6,7,8).

We have investigated alterations in adrenergic receptors and adenylate cyclase activity in cardiac membranes from rats injected with 40 mg/kg intraperitoneal isoproterenol. Reduction in the number of beta-adrenergic and alpha-adrenergic receptors, as assessed by changes in specific binding of 3H-dihydroalprenolol (DHA) and 3H-dihydroergocryptine (DHE), was observed only at 9 and 24 hours after isoproterenol injection, respectively. On the other hand, epinephrine-stimulated, NaF-stimulated, and Gpp (NH)p-stimulated adenylate cyclase activity was decreased as early as 3 hours after isoproterenol treatment without changes in the basal adenylate cyclase activity. These results demonstrate a defect in the adrenergic receptor-adenylate cyclase system during the development of catecholamine-induced cardiomyopathy and may partly explain the attenuated inotropic adrenergic response of the heart under stressful situations.