Effects of a selective DP receptor agonist (BW 245C) and antagonist (BW A868C) on the canine colonic epithelium: an argument for a different DP receptor?

Earlier studies showed that PGD2 produced both increases and decreases in short-circuit current across the canine proximal colon. PGD2 metabolites had opposing effects: 11 beta-PGF2 alpha elicited only increases in Isc, and 13,14-dihydro-15-keto-PGD2 elicited only decreases. The stimulant effects involved FP receptors, but the receptors involved in mediating the inhibitory effects remained undefined. Here we show that the tissue, although it is capable of producing both PGD2 and PGE2, did not produce 11 beta-PGF2 alpha in measurable amounts. The selective DP receptor agonist BW 245C did not mimic the inhibitory effects of PGD2, producing only dose-dependent increases in short-circuit current. Further, these responses were not significantly inhibited by BW A868C. Cross-desensitization experiments suggested that the stimulant effects of BW 245C involved the EP receptor. However, on a standard preparation (rabbit platelets), both PGD2 and BW 245C inhibited ADP-induced aggregation and were antagonized by BW A868C. 11 beta-PGF2 alpha had no effects. The decreases in short-circuit current across the canine colonic epithelium elicited by PGD2 and 13,14-dihydro-15-keto PGD2 are not mimicked by other prostanoids, nor by the selective agonist BW 245C, and thus appear to involve receptors other than the classical DP receptor.