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The antagonism by BW A868C of PGD 2 and BW245C activation of human platelet adenylate cyclase
Author(s) -
Trist D.G.,
Collins B.A.,
Wood J.,
Kelly M.G.,
Robertson A.D.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11817.x
Subject(s) - adenylate kinase , cyclase , antagonism , endocrinology , prostaglandin , medicine , chemistry , iloprost , platelet , prostaglandin d2 , prostacyclin , receptor , antagonist , biochemistry , biology
1 In glycerol‐lysed human platelets, prostaglandin D 2 (PGD 2 ) and the hydantoin BW245C both activate adenylate cyclase in a biphasic manner. These activations are qualitatively different from those of carbacyclin, iloprost and prostaglandin E 2 (PGE 2 ) whose E/[A] curves can be adequately described by rectangular hyperbolae. 2 Prostaglandin E 1 (PGE 1 ) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbola. 3 The selective PGD 2 antagonist BW A868C shifts the first phase of the PGD 2 and BW245C E/[A] curves but has no effect on the second phase. 4 Applying a two‐receptor model enables a pK B to be derived for BW A868C of 9.11. 5 BW A868C has no effect on carbacyclin, iloprost, prostacyclin, PGE 1 and PGE 2 at a concentration 1,000 fold that of its K B against PGD 2 and BW245C. 6 These results indicate that PGD 2 and BW245C are capable of activating adenylate cyclase in human platelets through the DP‐receptor and by another mechanism as yet uncharacterized.