Desensitization of α1 Adrenoceptor-Stimulated Glycogen Phosphorylase Activity in Vascular Smooth Muscle

Abstract

Summary

Desensitization of α1-adrenoceptor-mediated activation of glycogen phosphorylase was investigated in rabbit aorta. Activation of glycogen phosphorylase by epinephrine was antagonized by the α1-receptor selective antagonist prazosin but not by yohimbine (α1receptor selective) or by propranolol (β-receptor antagonist). Preincubation of rabbit aortic ring segments for 5 h with norepinephrine (NE, 10−5M) led to a 30-fold loss in sensitivity and a 55% decrease in maximal activation of the enzyme by a agonists. Preincubation of aortic ring segments with phenylephrine (10−5M) in the presence of propranolol (10−6M) also caused desensitization of glycogen phosphorylase activation. The desensitization was heterologous since maximal activation of the enzyme by histamine or KCl was also markedly diminished in segments preincubated with NE. In contrast to these results, catecholamine-induced desensitization to α1-adreno-ceptor-mediated smooth muscle contraction in aortic ring segments resulted in loss in sensitivity but not maximal force of contraction on subsequent stimulation by α1 agonists. These results suggest that the mechanism responsible for desensitization of glycogen phosphorylase is distal to receptor activation and may involve attenuation of responses to intracellular Ca2+ -dependent enzymes which have limited reserve.