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 sm ooth muscle and endothelium. The adenosine receptors mediating vasorel axations were characterized pharmacologically using isolated tissue ba th experiments. The rank order of potency of a series of adenosine ana logs for the vasorelaxations suggested the presence of multiple A(2)-t ype adenosine receptors both on the smooth muscle and endothelium of t he coronary artery. The smooth muscle At-type receptors were of two ty pes: one being xanthine-sensitive and activated by N-6- and C2-substit uted adenosine analogs, and the other xanthine-insensitive stimulated by 5'-uronamide derivatives. The endothelial A(2) adenosine receptors were xanthine-sensitive and were responsive to the 5'-uronamides. Thes e receptors were associated with the release of nitric oxide. Radiolig and binding studies using [(125)l]-APE and photoaffinity labeling with azide derivative of [I-125]-APE revealed a binding site corresponding to A(2A) receptor in membranes of porcine coronary artery smooth musc le. In addition, ligand binding with [H-3]-DPCPX demonstrated the exis tence of A(1) adenosine receptors in the porcine coronary artery smoot h muscle. These receptors were found to be linked to adenylate cyclase in an inhibitory manner via pertussis toxin-sensitive G protein(s), a nd could induce attenuation of vasorelaxation. In conclusion, the info rmation 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 ar e required to further characterize and delineate the roles of the vari ous adenosine receptors, and the information given herewith can provid e an impetus for this. (C) 1997 Wiley-Liss, Inc.