Coronary vasodilation by adenosine: Receptor subtypes and mechanism(s) of action

This article briefly reviews our recent findings regarding the status and functions of the adenosine receptors in porcine coronary artery smooth muscle and endothelium. The adenosine receptors mediating vasorelaxations were characterized pharmacologically using isolated tissue bath experiments. The rank order of potency of a series of adenosine analogs for the vasorelaxations suggested the presence of multiple A₂-type adenosine receptors both on the smooth muscle and endothelium of the coronary artery. The smooth muscle A₂-type receptors were of two types: one being xanthine-sensitive and activated by N⁶- and C2-substituted adenosine analogs, and the other xanthine-insensitive stimulated by 5'-uronamide derivatives. The endothelial A₂ adenosine receptors were xanthine-sensitive and were responsive to the 5'-uronamides. These receptors were associated with the release of nitric oxide. Radioligand binding studies using [¹²⁵I]-APE and photoaffinity labeling with azide derivative of [¹²⁵I]-APE revealed a binding site corresponding to A(2A) receptor in membranes of porcine coronary artery smooth muscle. In addition, ligand binding with [³H]-DPCPX demonstrated the existence of A₁ adenosine receptors in the porcine coronary artery smooth muscle. These receptors were found to be linked to adenylate cyclase in an inhibitory manner via pertussis toxin-sensitive G protein(s), and could induce attenuation of vasorelaxation. In conclusion, the information presented in this article generally suggests that the coronary artery contains various types of adenosine receptors that may play a role in the regulation of its function. However, additional studies are required to further characterize and delineate the roles of the various adenosine receptors, and the information given herewith can provide an impetus for this.