Antagonist pharmacology of adenosine A 2B receptors from rat, guinea pig and dog

Abstract

We have sought evidence for species differences between adenosine A 2B receptors by comparing the potencies of eight adenosine receptor antagonists, representing four different chemical classes, at the native adenosine A 2B receptors which mediate relaxation of smooth muscle from rat colon, guinea pig aorta and dog saphenous vein. In all three assays, the antagonists caused parallel rightward shifts in the concentration–response curves to NECA and there was no depression of the maximum responses. There were highly significant correlations between the p K B values on each of the three receptors. However, the p K B values of 8-SPT (8- p-(sulphophenyl)theophylline), XAC (8-[-[[[[(2-aminoethyl)amino]-carbonyl]methyl]oxy]phenyl]-1,3-dipropylxanthine), CGS 15943 (9-chloro-2,2-(furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine) and CGH 2473 N-[4-(3,4-dichloro-phenyl)-5-pyridin-4-yl-thiazol-2-yl]-acetamide) for the dog receptor exceeded by at least 0.5 log units the p K B values at the rat and guinea pig sites. Our data indicate species differences between the rat and guinea pig adenosine A 2B receptors on the one hand and the dog adenosine A 2B receptor on the other with respect to antagonist pharmacology.