Desensitization of beta adrenergic receptors linked to adrenocorticotropin secretion.
Stimulation of beta adrenergic receptors on AtT-20 cells increases intracellular cyclic AMP levels and adrenocorticotropin hormone (ACTH) release. Pretreatment of these cells with catecholamines reduces the ability of (-)-isoproterenol to stimulate both cyclic AMP formation and ACTH secretion. This beta receptor desensitization is time- and dose-dependent and is reversible. Various beta adrenergic agonists can induce this desensitization with a rank order of potency of salmefamol greater than or equal to (-)-isoproterenol greater than or equal to epinephrine greater than or equal to norepinephrine greater than or equal to (+)-isoproterenol. (+/-)-Propranolol but not practolol can block the (-)-isoproterenol-induced beta receptor desensitization. Long-term treatment of AtT-20 cells with (-)-isoproterenol reduces the density of beta receptors but does not affect the affinity of these sites for [3H]dihydroalprenolol. In addition to desensitizing beta receptors, (-)-isoproterenol pretreatment enhances basal ACTH secretion. This effect was dose-dependent and blocked by (+/-)-propranolol. Forskolin-stimulated cyclic AMP formation and ACTH secretion was not altered by (-)-isoproterenol treatment indicating that the desensitization of beta receptors on AtT-20 cells is the result of receptor-adenylate cyclase uncoupling. No cross-desensitization of corticotropin releasing factor or vasoactive intestinal peptide receptors occurred as (-)-isoproterenol treatment did not alter the effect of these peptides on cyclic AMP synthesis or ACTH secretion.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000648:ultrastructure; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D013268:Stimulation, Chemical; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D007545:Isoproterenol