The alpha adrenergic receptor mediated increase in guinea-pig liver glycogenolysis

Abstract

Amidephrine, a selective α-adrenergic receptor agonist, and isoprenaline, a selective β-receptor agonist, each produced comparable, dose related, increases in the glycogen phosphorylase activity of guinea-pig liver slices, while only isoprenaline produced a statistically significant increase in cyclic AMP levels. These effects were obtained with agonist concentrations which produced similar increases in the rate of glucose release. Although the tissue was only exposed to the drugs for 2 min. it is not thought likely that an earlier peak in cyclic AMP, caused by amidephrine, remained undetected, as the α-agonist did not stimulate adenylate cyclase in a membrane preparation from guinea-pig liver. The effect of amidephrine on phosphorylase activity was abolished by phentolamine at a concentration which did not affect the response to isoprenaline. It is concluded that α-receptor stimulation is as effective as β-receptor stimulation in increasing hepatic glycogenolysis, but that the α-mediated effects do not involve cyclic AMP. The possibility that α effects result from changes in phosphorylase kinase or phosphatase activity brought about by cellular calcium re-distribution is discussed.