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Therapeutic options in inflammatory bowel disease: experimental evidence of a beneficial effect of kinin B 1 receptor blockade
Author(s) -
Marceau F,
Regoli D
Publication year - 2008
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 - 10.1038/bjp.2008.233
Subject(s) - kinin , inflammatory bowel disease , receptor , inflammation , pharmacology , downregulation and upregulation , receptor antagonist , immunology , medicine , endocrinology , antagonist , chemistry , disease , biochemistry , bradykinin , gene
A surprising proportion of patients with inflammatory bowel disease (IBD) remain refractory to all classes of drugs presently in clinical use. Kinins are inflammatory mediators of potential relevance in IBD, because at least the kinin B 1 receptor subtype is upregulated in human or animal intestinal inflammation and also both B 1 and B 2 receptors for kinins support inflammation and epithelial electrogenic ion transport that leads to secretory diarrhoea. In this issue of the BJP , Hara et al . report the therapeutic effect of a modern and selective nonpeptide kinin B 1 receptor antagonist, SSR240612 ((2 R )‐2‐(((3 R )‐3‐(1,3‐benzodioxol‐5‐yl)‐3‐(((6‐
methoxy‐2‐naphthyl)sulphonyl)amino)propanoyl)amino)‐3‐(4‐((2 R ,6 S )‐
2,6‐dimethylpiperidinyl)methyl)phenyl)‐ N ‐isopropyl‐ N ‐
methylpropanamide hydrochloride), with benefits such as decreased neutrophil influx and improved macroscopic tissue scoring. The results were corroborated using kinin B 1 receptor gene‐knockout mice. Further, kinin B 1 receptor upregulation in this inflammatory model is partially dependent on TNF‐α, a recognized target for IBD pharmacotherapy. More work is warranted to evaluate the value of the kinin B 1 receptor antagonists as a novel anti‐inflammatory therapeutic option for IBD. British Journal of Pharmacology (2008) 154 , 1163–1165; doi: fn1 ; published online 9 June 2008