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

• Published in: British journal of pharmacology Vol. 112; no. 2; pp. 461 - 464
• Main Authors: Farmer, Stephen G., DeSiato, Mark A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-1994; Nature Publishing
• Subjects: Animals; antagonist; B2 receptor; B3 receptor; Biological and medical sciences; Bradykinin; Bradykinin - pharmacology; Bradykinin Receptor Antagonists; bradykinin receptors; Ferrets; Guinea Pigs; ileum; Ileum - drug effects; In Vitro Techniques; Male; Medical sciences; Methacholine Compounds - pharmacology; Muscle; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Naphthalenes - pharmacology; nonpeptide; Organophosphorus Compounds - pharmacology; Pharmacology. Drug treatments; smooth muscle; trachea; Trachea - drug effects; Trachea - metabolism; WIN 64338; Fissipedia; Carnivora; Rodentia; Smooth muscle; Muscle contraction; Ileum; Vertebrata; Mammalia; Guinea pig; Animal; Bradykinin; Ferret; Peptidergic receptor; Antagonist; Trachea
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1994.tb13095.x

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 μm, 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).