INTERACTION OF BW-A868C, A PROSTANOID DP-RECEPTOR ANTAGONIST, WITH 2 RECEPTOR SUBTYPES IN THE RABBIT ISOLATED SAPHENOUS-VEIN

In isolated rings of rabbit saphenous vein (RbSV) pre-contracted with 40 mM KCI, Prostaglandin E(2) (PGE(2)), BW245C (a DP-receptor agonist) and PGD(2) caused concentration-dependent relaxations with mean poten cies (EC(50)) of 0.5, 38 and 114 nM respectively. The DP-receptor anta gonist,BW A868C, antagonized BW245C concentration-effect (E/[A]) curve s, 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 pA(2) estimate of 5.1 obtained for BW A868C against PGE(2) was not statistically different to the lower pK( B) of 4-9- obtained against BW245C, and is probably indicative of anta gonism at the EP(4)-receptor. PGD, mediated responses were also antago nized by BW A868C, however the resultant E/[A] curves were 'bell shape d' in nature. The weak EP(4)-receptor antagonist AH23848B, also antago nized BW245C and PGD(2) responses, yielding pA(2) estimates of 5.6 and 5.5 respectively. These results suggest that in the RbSV, BW245C and PGD(2) are nonselective agonists mediating relaxations through DP- and EP(4)-receptors. BW A868C also displayed an affinity for DP-receptors in this preparation, in addition to a second receptor subtype, presum ably the EP(4)-receptor.