EVIDENCE FOR DISTINCT PROSTAGLANDIN-I2 AND PROSTAGLANDIN-D2 RECEPTORS IN HUMAN-PLATELETS

Abstract

Incubation of human platelet-rich plasma with prostaglandin [PG]I2, results in a marked increase in C[cyclic]AMP that persists for at least 60 min. The persistent stimulation of cAMP levels by PGI2 can be rapidly reversed by the addition of PGE1 or PGE2 but not by 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 desensitizes for consequent 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 PG antagonist N-0164[sodium-p-benzyl-4-[1-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. Human platelets evidently have distinct pharmacological receptors for PGI2 and PGD2 and PGE compounds may actually interact with a PGI2 receptor.