Functional Desensitisation of β‐Adrenergic Receptors of Avian Erythrocytes by Catecholamines and Adenosine 3′,5′‐Phosphate

Abstract

Prolonged exposure to .beta.-adrenergic agonists of pigeon erythrocytes causes a reversible loss (70%) of catecholamine-stimulated adenylate cyclase activity without reduction in the number of .beta.-adrenergic receptors. In addition a less pronounced decrease in non-stimulated and NaF-stimulated adenylate cyclase activity (15-22%) is observed, appearing at different agonist concentrations and at a different rate. Dibutyryl-cAMP and the phosphodiesterase inhibitor methylisobutylxanthine partially mimic the action of the .beta.-adrenergic agonist, pointing to a possible role of cAMP in establishing desensitization. When adenylate cyclase from desensitized cells is stimulated with 5''-guanylyl-imidodiphosphate in the presence or absence of catecholamines the lag period preceding the attainment of maximal activity is extended. The rate of reversal by GTP or ATP of persistent activation of adenylate cyclase is slowed down. The loss in hormonal stimulation on treatment of pigeon red blood cells with .beta.-adrenergic agonists is due to a delayed exchange of GDP against GTP on the regulatory GTP-binding protein. Events causing the refractory state in avian erythrocytes should occur at a site distal to the .beta.-adrenergic receptor.