DESENSITIZATION OF ADENYLATE-CYCLASE AND DOWN REGULATION OF BETA-ADRENERGIC RECEPTORS AFTER INVIVO ADMINISTRATION OF BETA-AGONIST

  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 327-331
Abstract
In vitro incubation of cells with catecholamines leads to both down-regulation of .beta.-adrenergic receptor number and desensitization of agonist-stimulated adenylate cyclase activity. These same parameters, were assessed in rat lung membranes after in vivo administration of metaproterenol, a .beta.2-selective agonist. In vivo treatment with metaproterenol leads to the following: reduced .beta.-adrenergic receptor number, reduced isoproterenol-stimulated adenylate cyclase activity, unaffected NaF or 5''-guanylylimidodiphosphate-stimulated adenylate cyclase activity, and reduced affinity of the receptor for isoproterenol similar to the affinity observed in the presence of 5''-guanylylimidodiphosphate. In vivo metaproterenol administration results in an uncoupled receptor-adenylate cyclase complex. The effects of in vivo administration of the glucocorticoid, methylprednisolone, to metaproterenol-pretreated animals were also assessed. Glucocorticoid treatment was associated with the following: increased .beta.-adrenergic receptor number in rats in which the receptors have been down-regulated, increased isoproterenol responsiveness in agonist-densensitized rats, and no effect on agonist affinity in desensitized animals. Evidently, the restoration of agonist responsiveness by glucocorticoids in the catecholamine refractive state is not simply a reversal of receptor down-regulation or adenylate cyclase desensitization.