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 PGD(2) produced both increases and decreas es in short-circuit current across the canine proximal colon. PGD(2) m etabolites had opposing effects: 11 beta-PGF(2 alpha) elicited only in creases in I-sc, and 13,14-dihydro-15-keto-PGD(2) elicited only decrea ses. The stimulant effects involved FP receptors, but the receptors in volved in mediating the inhibitory effects remained undefined. Here we show that the tissue, although it is capable of producing both PGD(2) and PGE(2), did not produce 11 beta-PGF(2 alpha) in measurable amount s. The selective DP receptor agonist BW 245C did not mimic the inhibit ory effects of PGD(2), producing only dose-dependent increases in shor t-circuit current. Further, these responses were not significantly inh ibited by BW A868C. Cross-desensitization experiments suggested that t he stimulant effects of BW 245C involved the EP receptor. However, on a standard preparation (rabbit platelets), both PGD(2) and BW 245C inh ibited ADP-induced aggregation and were antagonized by BW A868C. 11 be ta-PGF(2 alpha) had no effects. The decreases in short-circuit current across the canine colonic epithelium elicited by PGD(2) and 13,14-dih ydro-15-keto PGD(2) 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.