Stimulation of hepatic glycogenolysis by alpha 1- and beta 2-adrenergic agonists. Evidence against short term agonist-induced desensitization of the responses

Abstract

Addition of alpha 1-adrenergic agonists or vasopressin to the medium perfusing rat livers was associated with a rapid efflux of Ca2+, which was rapidly reaccumulated on removal of the stimulus. The magnitudes of the respective Ca2+ efflux and influx responses were similar, suggesting that Ca2+ was being mobilized from, and then reaccumulated into, the same pool(s). Addition of combinations of alpha 1-agonists, vasopressin and angiotensin II to isolated hepatocytes revealed that the Ca2+ efflux response induced by each individual hormone could only be augmented by addition of a second hormone when submaximal doses of each were employed. This suggests that an identical pool(s) of hepatocyte Ca2+ is mobilized in response to each of these agents. No desensitization of the alpha 1-adrenergic glycogenolytic response was observed in the perfused liver, upon repeated or more prolonged (25 min) exposure to agonist, providing cell Ca2+ reaccumulation occurred before addition of each successive stimulus. Selective short term stimulation of the beta 2-adrenergic glycogenolytic response in immature male rats (less than 150 g, body weight) was not associated with desensitization to subsequent stimulation. These data demonstrate that the glycogenolytic response of liver cells does not become desensitized by successive short term stimulation with alpha 1- or beta 2-adrenergic agonists.