AGONIST REGULATION OF THE HUMAN-PLATELET PROSTAGLANDIN-D2 RECEPTOR

The effect of exposing platelets to prostaglandin D2 (PGD2) on hormone binding was studied. Incubation of platelets with PGD2 for 2 hr resulted in a decrease in [3H]PGD2 binding that was dose dependent. Inhibition of binding was 14% after incubation with 10-8M PGD2, 19% after incubation with 10-7M PGD2, and 40% after exposure to 10-6M PGD2. This decreased binding (desensitization) was specific for [3H]PGD2 as binding to platelets by [3H]PGE1 and the α-adrenergic antagonist [3H] dihydroergocryptine (DHEC) was comparable to control platelets. Saturation of [3]PGD2 binding to desensitization platelets was at 27 fmole ligand/108 platelets compared to 43 fmoles/108 platelets in control platelets. Half-maximal saturation occured at 20 nM PGD2 both for desensitized and control platelets, suggesting that decreased binding sites rather than altered affinity between ligand and receptor accounted for these results. These platelets had a partial increase in [3H]PGD2 binding a few hours after plasma was washed free of PGD2 with complete resensitization after 24 hr. Since prostaglandins such as PGI2, PGD2, and PGE1 are potent inhibitors of platelet aggregation, decreased binding of platelets to these hormones after prostaglandin exposure may provide a mechanism for altered responsiveness of platelets to aggregating stimuli. © 1979.