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. 1994 Jun;112(2):461–464. doi: 10.1111/j.1476-5381.1994.tb13095.x

Effects of a novel nonpeptide bradykinin B2 receptor antagonist on intestinal and airway smooth muscle: further evidence for the tracheal B3 receptor.

S G Farmer 1, M A DeSiato 1
PMCID: PMC1910382  PMID: 8075864

Abstract

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 B2 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 pA2 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 B2 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 microM, 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 B2 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 (B3?) is different from that in ileal tissue (B2).

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Selected References

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