DESENSITIZATION OF BETA-ADRENERGIC RECEPTORS LINKED TO ADRENOCORTICOTROPIN SECRETION

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (1) , 107-114
Abstract
Stimulation of .beta.-adrenergic receptors on [mouse pituitary tumor] AtT-20 cells intracellular cAMP levels and ACTH release. Pretreatment of these cells with catecholamines reduces the ability of (-)-isoproterenol to stimulate both cAMP 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 .gtoreq. (-)-isoproterenol .gtoreq. epinephrine .gtoreq. norepinephrine .gtoreq. (+)-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 (.female.)-propranolol. Forskolin-stimulated cAMP 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 cAMP synthesis or ACTH secretion.

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