PGE1 and PGE2 modify platelet function through different prostanoid receptors

There is evidence that the overall effects of prostaglandin E2 (PGE2) on human platelet function are the consequence of a balance between promotory effects of PGE2 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 E1 (PGE1), 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 A2 mimetic U46619 to compare the effects of PGE1 and PGE2 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 PGE2 interacts with EP3 and EP4 receptors, but not IP receptors. In contrast PGE1 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.

Research highlights▶ The effects of PGE1 on platelet function are mediated by EP3 and IP receptors but not EP4. This is the first demonstration of the involvement of EP3 receptors in human platelet responses to PGE1. ▶ Confirmation of the effects of PGE2 on platelet function being mediated by EP3 and EP4 receptors but not IP. ▶ Effects of PGE1 and PGE2 on platelet function are the result of a balance between their actions at receptors which have opposing effects on adenylate cyclase. ▶ Blockade of the EP3 receptor enhances the ability of naturally occurring prostaglandins to inhibit platelet function.