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.