The alpha 1-agonist phenylephrine in hepatocytes from mature and senescent rats, and the beta-agonist isoproterenol in hepatocytes from senescent rats, elicited a time-dependent, homologous desensitization of alpha 1- and beta-receptor-mediated glycogenolysis respectively, which was maximal after 20 min of exposure to the agonists. Glucagon triggered desensitization of the glycogenolytic response to glucagon, isoproterenol and phenylephrine, which was maximal after less than 5 min; this was followed by resensitization of the glucagon response only. After 20 min of treatment with phenylephrine or isoproterenol, no change in cellular distribution of alpha 1- or beta-receptors was noticed, using sucrose gradient centrifugation. After a 1-h exposure to both agonists, 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 altered upon ageing. We conclude that functional desensitization and internalization of adrenergic receptors in rat hepatocytes are separate events in time and are largely unaffected by the ageing process. Thus, despite the absence of a beta-receptor-mediated glycogenolytic response in hepatocytes from mature rats, isoproterenol triggers the internalization of beta-receptors.
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