DESENSITIZATION OF ALPHA(1)-RECEPTOR, BETA-RECEPTOR AND GLUCAGON-RECEPTOR IN RAT HEPATOCYTES - INFLUENCE OF AGING

The alpha(1)-agonist phenylephrine in hepatocytes from mature and sene scent rats, and the beta-agonist isoproterenol in hepatocytes from sen escent rats, elicited a time-dependent, homologous desensitization of alpha(1)- and beta-receptor-mediated glycogenolysis respectively, whic h was maximal after 20 min of exposure to the agonists. Glucagon trigg ered desensitization of the glycogenolytic response to glucagon, isopr oterenol and phenylephrine, which was maximal after less than 5 min; t his was followed by resensitization of the glucagon response only. Aft er 20 min of treatment with phenylephrine or isoproterenol, no change in cellular distribution of alpha(1)- or beta-receptors was noticed, u sing sucrose gradient centrifugation. After a 1-h exposure to both ago nists, a shift of both receptors to a light density fraction was found , reflecting receptor internalization. Neither the rate of functional desensitization, nor the degree of receptor internalization was altere d upon ageing. We conclude that functional desensitization and interna lization of adrenergic receptors in rat hepatocytes are separate event s in time and are largely unaffected by the ageing process. Thus, desp ite the absence of a beta-receptor-mediated glycogenolytic response in hepatocytes from mature rats, isoproterenol triggers the internalizat ion of beta-receptors.