Defect in the adrenergic receptor-adenylate cyclase system during development of catecholamine-induced cardiomyopathy.
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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology
D011941:Receptors, Adrenergic; D004088:Dihydroergotoxine; D004082:Dihydroalprenolol; D012969:Sodium Fluoride; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004837:Epinephrine