Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro.
In vitro incubation of frog erythrocytes with (minus)-isoproterenol, 0.1 mM, at 23 degrees for 10 to 24 hours caused a 63% decline (rho less than 0.001) in the maximum (minus)-isoproterenol-stimulated adenylate cyclase activity in the erythrocyte membranes. Affinity for (minus)-isoproterenol as judged by the concentration which half-maximally stimulated the enzyme was not markedly altered. Basal enzyme activity and stimulation by fluoride or prostaglandin E1 remained unaltered. The number of beta-adrenergic receptor binding sites, assessed by binding studies with the beta-adrenergic antagonist (minus)-[3-H] alprenolol, declined by 50% (rho less than 0.005) in the (minus)-isoproterenol-treated cells. The binding affinity of the sites was not changed. Regulation of the concentration of functionally active beta-adrenergic receptors in membranes may be one of the mechanisms by which chronic exposure to catecholamines desensitizes tissues to beta-adrenergic stimulation.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000526:Alprenolol / Q000378:metabolism; D000818:Animals; D001001:Anura; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008024:Ligands; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D011941:Receptors, Adrenergic; D011956:Receptors, Cell Surface; D014316:Tritium
D008024:Ligands; D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011956:Receptors, Cell Surface; D014316:Tritium; D000526:Alprenolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol