title: Partial agonist effects of BW A868C, a selective DP receptor antagonist, on Cl- secretion in dog tracheal epithelium.
abstract: We examined the interactions of prostaglandin D2, BW245C ((+/-)-5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)-hydantoin) a selective DP receptor agonist and BW A868C ((+/-)-3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2- hydroxyethylamino)-hydantoin) a selective DP receptor antagonist on Cl- secretion using dog isolated tracheal epithelial preparations in Ussing chambers. Both prostaglandin D2 and BW245C stimulated Cl- secretion as reflected by increased short-circuit current (Isc) in the epithelial cells where the latter was more potent than the former. BW A868C produced, consistently, weak but significant partial agonism on Cl- secretion in these preparations in addition to its expected antagonism at the DP receptors. A pKB estimate of 8.16 +/- 0.06 (n = 11) for BW A868C from its antagonism to BW245C was found to be comparable with its estimates of both p[A]50 (8.19 +/- 0.14, n = 5) and pKA (8.00 +/- 0.20, n = 5). In addition, no significant effect by BW A868C up to 1 microM on Cl- secretory responses to other prostanoids, such as prostaglandin E2, prostaglandin F2 alpha and 9 alpha, 11 beta-prostaglandin F2 alpha, was detected in the system. These results are consistent with previous findings that BW A868C is a selective antagonist at the DP receptors mediating Cl- secretion by epithelial cells. To our knowledge, this is a (the first) confirmation of partial agonist properties of BW A868C in an isolated tissue system.
authors.affiliation: Department of Pharmacology, Astra Charnwood, Loughborough, Leicestershire, UK.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liu
authors.forename: D M
authors.initials: DM
authors.lastname: Jackson
authors.forename: A
authors.initials: A
authors.lastname: Blackham
authors.forename: P
authors.initials: P
authors.lastname: Leff
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D004285:Dogs; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006827:Hydantoins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D011457:Prostaglandins D / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002712:Chlorides; D006827:Hydantoins; D011457:Prostaglandins D; D011982:Receptors, Prostaglandin; C058848:BW A868C; C030669:BW 245C