PARTIAL AGONIST EFFECTS OF BW A868C, A SELECTIVE DP RECEPTOR ANTAGONIST, ON CL- SECRETION IN DOG TRACHEAL EPITHELIUM

We examined the interactions of prostaglandin D-2, BW245C (( hexyl)-1- (3-cyclohexyl-3-hydroxypropyl)-hydantoin) a selective DP receptor agon ist and BW A868C yl)-1-(2-cydohexyl-2-hydroxyethylamino)-hydantoin) a selective DP receptor antagonist on Cl- secretion using dog isolated t racheal epithelial preparations in Ussing chambers. Both prostaglandin D-2 and BW245C stimulated Cl- secretion as reflected by increased sho rt-circuit current (I-sc) in the epithelial cells where the latter was more potent than the former. BW A868C produced, consistently, weak bu t significant partial agonism on Cl- secretion in these preparations i n addition to its expected antagonism at the DP receptors. A pK(B) est imate of 8.16 /- 0.06 (n = 11) for BW A868C from its antagonism to BW2 45C was found to be comparable with its estimates of both p[A](50) (8. 19 +/- 0.14, n = 5) and pK(A) (8.00 +/- 0.20, n = 5). In addition, no significant effect by BW A868C up to 1 mu M on Cl- secretory responses to other prostanoids, such as prostaglandin E(2), prostaglandin F-2 a lpha and 9 alpha, 11 beta-prostaglandin F-2 alpha, was detected in the system. These results are consistent with previous findings that BW A 868C is a selective antagonist at the DP receptors mediating Cl- secre tion by epithelial cells. To our knowledge, this is a (the first) conf irmation of partial agonist properties of BW A868C in an isolated tiss ue system.