Effect of thromboxane antagonists on prostaglandin regulation of platelet adenylate cyclase.

Abstract

Platelet adenylate cyclase appears to be regulated through separate stimulatory and inhibitory prostaglandin receptors. To test the possibility that the inhibitory receptor represents overlap with a thromboxane A2 receptor the effect of thromboxane antagonists on prostaglandin regulation of adenylate cyclase was examined. Neither 13-azaprostanoic acid nor SQ29,548 had any effect on prostaglandin-mediated cyclic AMP regulation in intact platelets, while pinane thromboxane A2 and carbocyclic thromboxane A2 exhibited behavior consistent with these compounds acting as agonists at the inhibitory prostaglandin site. Because of the divergent behavior of the two groups of thromboxane antagonists it is unclear whether the inhibitory prostaglandin site represents a thromboxane site. It seems clear, however, that PTA2 and CTA2 represent pure agonists at the prostaglandin inhibitory site, showing little, if any, overlap with the stimulatory site, and therefore represent useful compounds for the study of prostaglandin regulation of platelet adenylate cyclase, providing additional evidence for the existence of a distinct prostaglandin inhibitory site.