PGE 1 and PGE 2 modify platelet function through different prostanoid receptors

Abstract

There is evidence that the overall effects of prostaglandin E 2 (PGE 2) on human platelet function are the consequence of a balance between promotory effects of PGE 2 acting at the EP3 receptor and inhibitory effects acting at the EP4 receptor, with no role for the IP receptor. Another prostaglandin that has been reported to affect platelet function is prostaglandin E 1 (PGE 1), however the receptors that mediate its actions on platelet function have not been fully defined. Here we have used measurements of platelet aggregation and P-selectin expression induced by the thromboxane A 2 mimetic U46619 to compare the effects of PGE 1 and PGE 2 on platelet function. Their effects on vasodilator-stimulated phosphoprotein (VASP) phosphorylation, as a marker of cAMP, were also determined. We also investigated the ability of the selective prostanoid receptor antagonists CAY10441 (IP antagonist), DG-041 (EP3 antagonist) and ONO-AE3-208 (EP4 antagonist) to modify the effects of the prostaglandins on platelet function. The results obtained confirm that PGE 2 interacts with EP3 and EP4 receptors, but not IP receptors. In contrast PGE 1 interacts with EP3 and IP receptors, but not EP4 receptors. In both cases the overall effects on platelet function reflect the balance between promotory and inhibitory effects at receptors that have opposite effects on adenylate cyclase.