IDENTIFICATION OF ALPHA ADRENOCEPTOR SUBTYPES IN DOG ARTERIES BY (H-3) YOHIMBINE AND (H-3) PRAZOSIN

Binding of the .alpha.-adrenergic antagonists (3H)prazosin and (3H) yohimbine to membranes of dog arteries exhibit the characteristics expected of .alpha.-adrenoceptors. Binding of both ligands is saturable with Kd of 0.19 and 1.15 nM for (3H)prazosin and (3H)yohimbine, respectively. A series of catecholamines inhibit binding of both ligands with a potency in the order epinephrine > norepinephrine .times. isoproterenol, corresponding with the activity of these agents at .alpha.-adrenoceptors in blood vessels. Competition for binding in both instances is stereoselective. l-Phenylephrine has similar potencies in inhibiting (3H)prazosin and (3H)yohimbine specific binding while the imidazoline related partial .alpha.-adrenergic agonists clonidine and guanfacine are more potent in inhibiting (3H)yohimbine specific binding. The affinity of prazosin for the (3H)yohimbine binding site is .apprx. 2500 times less than for the (3H)prazosin site while yohimbine is .apprx. 150 times more potent in inhibiting (3H)yohimbine than (3H)prazosin specific binding. Non-selective .alpha.-adrenergic antagonists have similar affinities for both binding sites. The concentrations of (3H)yohimbine binding sites in different arteries vary .apprx. 2-fold while for (3H)prazosin the variation was .apprx. 3-fold. There are 2 discrete noradrenergic binding sites in the major arteries of dog which have binding properties expected of .alpha.1- and .alpha.2-adrenoceptors.