Interrelation of prostaglandin endoperoxide (prostaglandin G2) and cyclic 3',5'-adenosine monophosphate in human blood platelets

Abstract

The prostaglandin endoperoxide, prostaglandin G2, in platelet-rich plasma may produce reversible platelet aggregation without secretion, irreversible aggregation with secretion of platelet constituents inhibited by indomethacin, or the latter effects despite indomethacin, depending on the concentration of the endoperoxide. Irreversible aggregation and platelet secretion induced by prostaglandin G2 apparently result from the action of ADP, since these responses are inhibited by 2-n-amylthio-5'-AMP (an inhibitor of the actions of ADP on platelets) and they do not occur in heparinized platelet-rich plasma. Prostaglandin G2 lowers the platelet level of cyclic 3',5'-AMP. Its actions are inhibited by elevation of cyclic AMP levels by prostaglandin E1 or dibutyryl cyclic AMP or adenosine. Like malondialdehyde production induced by thrombin, ADP, or arachidonic acid, prostaglandin G2-induced malondialdehyde production is reduced by dibutyryl cyclic AMP and prostaglandin E1. Platelet activation by prostaglandin G2 is enhanced by the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)-adenine. The action of prostaglandin G2 on platelets is more complex then previously reported.