LIGAND SELECTIVITY OF DOG CORONARY ADENOSINE RECEPTOR RESEMBLES THAT OF ADENYLATE-CYCLASE STIMULATORY (RA) RECEPTORS

Abstract

Adenosine receptors on the surface of coronary myocytes initiate coronary relaxation, but events subsequent to receptor occupancy are uncertain. The coronary vasoactivity of receptor-selective adenosine analogs was assayed in open chest dogs to test the hypothesis that the coronary adenosine receptor is an adenylate cyclase stimulatory (Ra) receptor. The potency order was: ethyl adenosine-5''-uronamide > cyclopropyl adenosine-5''-uronamide > 2-chloroadenosine > N6-[R(-)-1-phenyl-2-propyl]adenosine (R-PIA) > N6-cyclohexyladenosine > adenosine > S-PIA. Such a hierarchy of activity resembles that of the Ra receptors of thyroid and aortic myocyte adenylate cyclases and of tracheal smooth muscle relaxation. The potency order R-PIA > adenosine and the stereoselective coronary vasoactivity of R-PIA suggest that the coronary receptor may be a hybrid receptor which contains the N6 site typical of inhibitory (Ri) receptors in addition to the 5''-uronamide site which expresses Ra activity.