Partial agonist effects of BW A868C, a selective DP receptor antagonist, on Cl- secretion in dog tracheal epithelium
| Autor: | D.M. Jackson, Yu J. Liu, Alan Blackham, P. Leff |
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| Rok vydání: | 1996 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class medicine.medical_treatment Receptors Prostaglandin Prostaglandin In Vitro Techniques Partial agonist Models Biological Epithelium chemistry.chemical_compound Dogs Chlorides Internal medicine medicine Animals Drug Interactions Receptor Pharmacology Prostaglandins D Hydantoins Antagonist Trachea Endocrinology chemistry Female Prostaglandin D2 Antagonism Prostaglandin E |
| Zdroj: | European journal of pharmacology. 304(1-3) |
| ISSN: | 0014-2999 |
| Popis: | We examined the interactions of prostaglandin D 2 , 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 D 2 and BW245C stimulated Cl − secretion as reflected by increased short-circuit current ( I sc ) 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 p K B 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 p K A (8.00 ± 0.20, n = 5). In addition, no significant effect by BW A868C up to 1 μM on Cl − secretory responses to other prostanoids, such as prostaglandin E 2 , prostaglandin F 2α and 9α,11β-prostaglandin F 2α , 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. |
| Databáze: | OpenAIRE |
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