Evidence for two Separate Receptors Mediating the Stimulation of Platelet Adenylate Cyclase by Prostaglandin I₂ (PCI₂), PGD₂ and PCE₁

Prostacyclin (PGI₂), and prostaglandins D₂ and E₁, all inhibit aggregation of human platelets by stimulating adenylate cyclase. In platelets prelabelled with ¹⁴C adenine, PGI₂ has a higher intrinsic activity than either PGD₂ or PGE_1α, as well as a higher apparent affinity. PGE₁, but not PGD₂, inhibits the action of high concentrations of PGI₂, both when added simultaneously with PGI₂ and when added 3 min later. In the latter case the slow spontaneous fall in intracellular cyclic AMP Is accelerated by PGEj but not by PCD₂. PGF₂, at concentrations up to 100 μM neither stimulated the cyclase by itself, nor did it Inhibit the effects of PGI₂, PCE, or PCD₂. PCF_2α which did cause a small increase in cyclic AMP, inhibited PGD₂ strongly, PGE₁ not at all, and PCI₂ slightly at high concentrations. N0164, an inhibitor of aggregation induced by bls-enoic prostaglandins, inhibited cyclase stimulation by PGD₂ but not by PGE₁, PGE₂, PGD₁, or PGI₂, though it reduced PGI₂-induced inhibition of platelet aggregation. Preaddition of PGE₁, but not of PG₂, or PGD₂, at submaximal concentrations, inhibited subsequent response to high dose PGI₂. The results suggest chat PGE₁ and PCD₂ probably act on the same enzyme, but through a different receptor. PGE₁ acts as a partial agonist for the receptor for PCI₂, but In addition causes a tachyphylaxis not seen with PCI₂, or with, PGD₂.