ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE RAT VENTRICULAR MUSCLE

Scatchard analyses of [H-3]prazosin binding in rat ventricular muscle membranes showed biphasic curves, which identified alpha(1High)- and alpha(1Low)-affinity sites. The alpha(1High)-affinity site was completely inhibited by 1-mu-m phenoxybenzamine. The displacement potencies of alpha(1)-adrenergic antagonists were characterized by [H-3]prazosin binding to alpha(1High)- and alpha(1Low)-affinity sites in the absence and presence of 1-mu-M phenoxybenzamine. The affinities of most chemicals for alpha(1Low)-affinity sites were significantly lower than those for alpha(1High)-affinity sites, but WB-4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane), arotinolol, cinanserin, nifedipine, and p-aminoclonidine had the same affinities for both alpha(1Low)- and alpha(1High)-affinity sites. These results show that two alpha(1)-adrenoceptor subtypes, alpha(1High)- and alpha(1Low)-affinity, are present in the rat heart, and that there are physical variations in alpha(1)-adrenoceptor binding sites, based on their selectivity to antagonists.