On the multiplicity of platelet prostaglandin receptors. II. The use of N-0164 for distinguishing the loci of action for PGI2, PGD2, PGE2 and hydantoin analogs.
The omega-chain variant analogs of prostacyclin (PGI2) and PGD2 in which n-amyl side-chain has been replaced by a cyclohexyl group have been prepared and their cardiovascular activities have been compared to those of BW-245C(Fig. 1) a potent anti-aggregatory vasodilator bearing a cyclohexyl-terminated side-chain on a hydantoin skeleton. The cyclohexyl group has little effect on PGI2, but converts PGD2 to a long lasting hypotensive agent and increases the platelet anti-aggregatory potency of PGD2 by a factor of 8. The prostaglandin antagonist N-0164 selectively blocks the anti-aggregatory actions of PGD2, cyclohexyl-PGD2, and BW-245C; with essentially no effect on PGI2, cyclohexyl-PGI2 and PGE2 at comparably effective doses. The latter observation is contrary to an earlier report by MacIntyre, but supports the view that the anti-aggregatory effect of high doses of PGE2 (EC50=50 microM) is mediated by the PGI2 receptor. The hydantoin acts at the platelet PGD2 receptor.
D001792:Blood Platelets / Q000378:metabolism*; D015232:Dinoprostone; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D006827:Hydantoins / Q000378:metabolism* / Q000494:pharmacology; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000378:metabolism*; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000378:metabolism*; D011457:Prostaglandins D / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006827:Hydantoins; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; C012641:N 0164; C030669:BW 245C; D011464:Epoprostenol; D015232:Dinoprostone; D015230:Prostaglandin D2