Premium
Effects of a novel nonpeptide bradykinin B 2 receptor antagonist on intestinal and airway smooth muscle: further evidence for the tracheal B 3 receptor
Author(s) -
Farmer Stephen G.,
DeSiato Mark A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13095.x
Subject(s) - bradykinin , guinea pig , antagonist , competitive antagonist , bradykinin receptor , medicine , receptor antagonist , receptor , endocrinology , muscarinic acetylcholine receptor , ileum , histamine , biology , chemistry , pharmacology
1 We examined the effects of phosphonium, [[4‐[[2‐[[ bis (cyclohexylamino)methylene] amino]‐3‐(2‐naphthalenyl) 1‐oxopropyl]amino]‐phenyl]‐tributyl, chloride, monohydrochloride (WIN 64338), a novel, nonpeptide bradykinin B 2 receptor antagonist, on bradykinin‐induced contractions of guinea‐pig isolated ileum, and guinea‐pig and ferret trachea. 2 WIN 64338 potently and competitively antagonized ileal contractions, in response to bradykinin, exhibiting a pA 2 value of 7.97 ± 0.10. The compound was without effect on contractions elicited by methacholine, a muscarinic receptor antagonist. Thus, WIN 64338 is a competitive and selective antagonist of ileal B 2 receptors. 3 In contrast, WIN 64338 was completely without effect on bradykinin‐induced contractions of guinea‐pig or ferret trachea. Thus, even at a concentration of 1 μ m , which was sufficient to cause a 100 fold decrease in ileal sensitivity to bradykinin, WIN 64338 failed to shift the bradykinin log concentration‐response curves in trachea isolated from either species. 4 These data confirm that WIN 64338 represents the first reported nonpeptide antagonist of guinea‐pig ileal B 2 receptors. They also provide additional evidence for heterogeneity of bradykinin receptors within the same species (guinea‐pig) and, furthermore, indicate that the tracheal bradykinin receptor (B 3 ?) is different from that in ileal tissue (B 2 ).