The antagonism by BW A868C of PGD2 and BW245C activation of human platelet adenylate cyclase

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Abstract
In glycerol‐lysed human platelets, prostaglandin D2 (PGD2) and the hydantoin BW245C both activate adenylate cyclase in a biphasic manner. These activations are qualitatively different from those of carbacyclin, iloprost and prostaglandin E2 (PGE2) whose E/[A] curves can be adequately described by rectangular hyperbolae. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbola. The selective PGD2 antagonist BW A868C shifts the first phase of the PGD2 and BW245C E/[A] curves but has no effect on the second phase. Applying a two‐receptor model enables a pKB to be derived for BW A868C of 9.11. BW A868C has no effect on carbacyclin, iloprost, prostacyclin, PGE1 and PGE2 at a concentration 1,000 fold that of its KB against PGD2 and BW245C. These results indicate that PGD2 and BW245C are capable of activating adenylate cyclase in human platelets through the DP‐receptor and by another mechanism as yet uncharacterized.