Effects of adenosine analogs on inositol 1,4,5-trisphosphate production in porcine coronary artery

Abstract

Using various pharmacological methods, we previously demonstrated that the smooth muscle and endothelium of porcine coronary artery contain vasorelaxant adenosine A 2 receptors, which are predominantly the A 2A subtype. The present study was intended to investigate the effect of adenosine receptor stimulation on agonist-induced inositol 1,4,5-trisphosphate (IP 3) generation in porcine coronary artery using the nonselective adenosine analogs, 2-chloroadenosine (CAD) and 5′-( N-ethylcarboxamido)adenosine (NECA), and the A 2A selective analog 2- p-(2-carboxyethyl)-phenethylamino-5′- N-ethylcarboxamidoadenosine (CGS). In both endothelium-intact and denuded coronary artery rings, CAD, NECA and CGS elicited a dose-dependent inhibition of prostaglandin F 2α (PG)-induced IP 3 production. However, the inhibitory effect of NECA was relatively less in endothelium-denuded preparations. The nonselective xanthine adenosine receptor antagonist, 8-sulfophenyltheophylline (8-SPT), significantly attenuated the IP 3-inhibitory effect of CAD and, to a lesser extent, that of NECA. Further, the A 2A selective nonxanthine antagonist, 5-amino-7-(2-phenylethyl)-2-(-furyl)-pyrazolo[4,3]-1,2,4-triazolo[1,5- c]pyrimidine (SCH), markedly decreased the effects of all CAD, NECA and CGS on PG-induced IP 3 generation. These results provide evidence that activation of adenosine A 2 receptors by CAD, NECA and CGS in porcine coronary artery causes inhibition of agonist-induced IP 3 production, and these receptors involve at least the A 2A subtype.