Characterization of Postsynaptic Alpha-Adrenergic Receptors by [H]-Dihydroergocryptine Binding in Muscular Arteries from the Rat Mesentery

Alpha-adrenergic receptors are likely to be Important determinants of the effects of catecbolamines on rascular resistance. To study the a-adrenergic receptor in muscular arteries of the type that determine vascular resistance, we characterized and qnantitated a-adrenergk receptors in a partknlate fraction of the highly reactive, richly Innervated arteries of the rat mesentery. With the ligand ['HJ-dlhydroergocryptine ([•HJ-DHEC), specific binding (dlsplaceable by S /iM pbentolamioe) Is saturable. There is a single claw of binding sites with a dissociation constant (K*) of 2.9 nM and a maximal binding capacity of 68 fmoles of ['HJDHEC per mg of participate fraction protein. Catecholamlnes compete for ['HJ-DHEC binding stereospedfically and with the a-adrenergic potency series of (-)epinephrine > (-)norepinephrine > (-)isoproterenol. Binding is rapid (t Vt £ 2 mins) and rapidly rerersible (t Vi £ 2 mins). Inhibition of ['HJ-DHEC binding by the a-adrenergic antagonist pbentolamute (K,, 3.0 nM) is much greater than by the /3-adrenergk antagonist propranolol (Kd = 8200 nM). The a,-selective antagonist prazosin (Ka 63 nM) is 20 times more potent in competing for ['HJ-DHEC binding than is the a^selecthe antagonist yohimblne (Kj 1250 nM), thus suggesting that the a-adrenergk receptor identified is predominantly of the a, subtype that is responsible for vascular smooth muscle contraction. This extension of radiollgand binding techniques to highly innervated muscular arteries of the type contributing to rascular resistance will allow the study of the role of the vascular a-adrenergic receptor in various physiologic states and models of hypertension. (Hypertension 2: 149-155, 1980)