Effects of BW A868C, a Selective Prostaglandin DP Receptor Antagonist, in Dog Isolated Vascular Preparations

The effects of the selective prostaglandin DP receptor antagonist BW A868C ((+/-)-3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethylamin o)- hydantoin), 3.0 nM to 0.3 microM) were examined against prostaglandin D2 and BW245C ((+/-)-5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin)-in duced smooth muscle relaxation on dog isolated vascular preparations pre-contracted with a sub-maximal concentration of KCl (50 mM). In dog dorsal nasal vein BW245C was found to be more potent than prostaglandin D2 with p[A]50 estimates of 7.6 +/- 0.1 (S.E.M., n = 8) and 5.8 +/- 0.1 (n = 5), respectively. BW A868C, up to 0.3 microM, displaced the relaxant concentration-effect curves to BW245C in dog dorsal nasal vein in an apparently competitive manner with parallel rightward shifts and no significant changes in the upper asymptotes. The data were analysed by using a modified Schild equation which not only gives equal weight to all agonist concentration-effect data but also allows a direct plot in Clark plot space. A pKB estimate of 7.3 +/- 0.8 (n = 20) was obtained with a unity Schild plot slope (b = 1.0 +/- 0.1). This affinity estimate, however, is lower than the values previously reported in other studies. The affinity estimates of BW A868C against BW245C and prostaglandin D2 obtained from dog dorsal nasal vein, major palatine artery and saphenous vein were found to be consistent. The relatively low affinity estimates of BW A868C at DP receptors as observed in the present study may be due to species- or tissue-related variations or may be indicative of the possible existence of DP receptor subtypes.