Evidence for distinct prostaglandin I2 and D2 receptors in human platelets.
Incubation of human platelet-rich plasma with prostaglandin I2 (PGI2), results in a marked increase in adenosine 3':5'-monophosphate (cAMP) that persists for at least 60 min. The persistent stimulation of cAMP levels by PGI2 can be rapidly reversed by the addition of either prostaglandin E1 or E2 (PGE1, PGE2), but not by prostaglandin D2 (PGD2). Studies of agonist-specific desensitization of cAMP accumulation show that PGE1 or PGE2 can desensitize for subsequent PGE or PGI2 activation, and that subthreshold levels of PGI2 desensitize for subsequent PGE1 stimulation. PGD2 desensitizes for consequent PGD2 activation, but not for PGE1, PGE2 or PGI2, and PGE compounds and PGI2 do not desensitize for subsequent PGD2 activation. Agonist-specific desensitization for PGI2 is not dependent on cAMP accumulation, but appears to be a consequence of receptor occupation. Support of the desensitization experiments was obtained through the use of the prostaglandin antagonist N-0164 [sodium-p-benzyl-4-[-oxo-2-(4-chlorobenzyl)-3-phenyl-propyl]phenyl phosphonate). This compound proved to be a potent antagonist of PGD2 and a weak antagonist of PGI2-stimulated cAMP accumulation. These data indicate that human platelets have distinct pharmacological receptors for both PGI2 and PGD2, and that PGE compounds may actually interact with a PGI2 receptor.
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood; D004347:Drug Interactions; D011464:Epoprostenol / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D011453:Prostaglandins / Q000097:blood*; D011457:Prostaglandins D / Q000097:blood* / Q000494:pharmacology; D011458:Prostaglandins E / Q000097:blood / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013997:Time Factors
D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D011464:Epoprostenol; D000242:Cyclic AMP