β-Adrenergic Receptor: Stereospecific Interaction of Iodinated β-Blocking Agent with High Affinity Site

Abstract

An iodine-labeled β-adrenergic inhibitor (¹²⁵l-hydroxybenzylpindolol) binds specifically to a site on turkey erythrocyte membranes. A series of β-adrenergic agonists and inhibitors compete for this binding site, with apparent affinities paralleling biological effectiveness as activators or inhibitors of catecholaminestimulated adenylate cyclase. The activity of d-(+) agonists or inhibitors was 1 percent (or less) than that of the corresponding l-(-) isomers in competing for binding of the iodinated blocker as well as in affecting catecholamine-stimulated adenylate cyclase. 1-(-)-Norepinephrine was about one-tenth as active as l-(-)-isoproterenol in competing for the β-blocking agent site. The stereospecificity of the interaction with the iodinated β-blocking agent and the correspondence between affinity for site and biological potency of analogs suggested that this interaction is involved in function of the β-adrenergic receptor.