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. We assayed the coronary vasoactivity of receptor-selective adenosine analogs 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 greater than cyclopropyl adenosine-5'-uronamide greater than 2-chloroadenosine greater than N6-[R(-)-1-phenyl-2-propyl] adenosine (R-PIA) greater than N6-cyclohexyladenosine greater than adenosine greater than 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 greater than 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.