Desensitization of beta 2-adrenergic receptors and adrenocorticotropin release.
Pre-exposure of mouse anterior pituitary tumor cells (A+T-20/D16-16) to (-) isoproterenol reduces the ability of this beta-adrenergic agonist to restimulate cyclic AMP synthesis or adrenocorticotropin hormone (ACTH) release from these cells. This beta-adrenergic receptor desensitization is time and dose-dependent, recoverable and specific for beta-receptors. Longer pretreatment times are required to decrease beta-receptor density than to induce receptor desensitization. This initial beta-receptor refractoriness involves an uncoupling of the receptor from adenylate cyclase since (-) isoproterenol treatment does not alter forskolin-activated cyclic AMP formation or ACTH release. In addition to diminishing beta-receptor responsiveness, (-) isoproterenol treatment induces a prolonged elevation of basal ACTH release. This finding indicates that the intracellular events leading to ACTH secretion may also be altered during the desensitization process.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D004224:Diterpenes; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D004082:Dihydroalprenolol; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D007545:Isoproterenol