Antagonism of coronary artery relaxation by adenosine A(2A)-receptor antagonist ZM241385

We have tested the existence of functional A(2A) adenosine receptor in porcine coronary artery using, for the first time, the new A(2A) antagonist ZM241385. Nonselective agonist NECA and A(2A)-selective agonist CGS21680 produced concentration-dependent relaxation of prostaglandin F(2)α, (PGF(2α))precontracted endothelium intact (E⁺) and denuded (E^-) rings. Relaxation was significantly greater in E⁺ rings than in E^-rings. A(2A) adenosine receptor-selective antagonist, ZM241385 (10^-6 M), significantly attenuated the relaxation responses. The antagonism of ZM241385 was compared with that of SCH58261 (10^-6 M), another A(2A) adenosine receptor-selective antagonist, which also significantly attenuated the relaxation response to both agonists. However, ZM241385 produced a significantly greater shift of the relaxation-response curves to the right compared with SCH58261 both in E⁺ and E- rings. The data show for the first time that ZM241385 is a potent A(2A)-receptor antagonist in porcine coronary artery and a useful tool to study A(2A)-receptor function.