Identification of alpha adrenoceptor subtypes in dog arteries by (3H) yohimbine and (3H) 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 dissociation constants of 0.19nM and 1.15nM for (3H)prazosin and (3H)yohimbine respectively. A series of catecholamines inhibit binding of both ligands with a potency in the order epinephrine greater than norepinephrine much greater than 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 whilst 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 approximately 2500 times less than for the (3H)prazosin site whilst yohimbine is approximately 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 concentration of (3H)yohimbine binding sites in different arteries vary about two fold whilst for (3H)prazosin in the variation was about three fold. These results indicate that there are two discrete noradrenergic binding sites in the major arteries of dog which have binding properties expected of alpha 1 and alpha 2 adrenoceptors.