Interaction of BW A868C, a prostanoid DP-receptor antagonist, with two receptor subtypes in the rabbit isolated saphenous vein

In isolated rings of rabbit saphenous vein (RbSV) pre-contracted with 40 mM KCl, Prostaglandin E₂ (PGE₂), BW245C (a DP-receptor agonist) and PGD₂ caused concentration-dependent relaxations with mean potencies (EC₅₀) of 0.5, 38 and 114 nM respectively.The DP-receptor antagonist, BW A868C, antagonized BW245C concentration-effect ( ) curves, although the corresponding Schild plot had a slope less than unity and displayed a clear inflection. Analysis of the data yielded two pK_B estimates of 8.5 and 4.9, the higher estimate being consistent with antagonism at DP-receptors. The pA₂ estimate of 5.1 obtained for BW A868C against PGE₂ was not statistically different to the lower pK_B of 4.9 obtained against BW245C, and is probably indicative of antagonism at the EP₄-receptor. PGD₂ mediated responses were also antagonized by BW A868C, however the resultant curves were ‘bell shaped’ in nature. The weak EP₄-receptor antagonist AH23848B, also antagonized BW245C and PGD₂ responses, yielding pA₂ estimates of 5.6 and 5.5 respectively.These results suggest that in the RbSV, BW245C and PGD₂ are nonselective agonists mediating relaxations through DP- and EP₄-receptors. BW A868C also displayed an affinity for DP-receptors in this preparation, in addition to a second receptor subtype, presumably the EP₄-receptor.