作者
Rink-Jan Lohman, Adam J Cotterell, Jacky Suen, Ligong Liu, Anh T Do, David A Vesey, David P Fairlie
发表日期
2012/2/1
期刊
Journal of Pharmacology and Experimental Therapeutics
卷号
340
期号
2
页码范围
256-265
出版商
American Society for Pharmacology and Experimental Therapeutics
简介
Many trypsin-like serine proteases such as β-tryptase are involved in the pathogenesis of colitis and inflammatory bowel diseases. Inhibitors of individual proteases show limited efficacy in treating such conditions, but also probably disrupt digestive and defensive functions of proteases. Here, we investigate whether masking their common target, protease-activated receptor 2 (PAR2), is an effective therapeutic strategy for treating acute and chronic experimental colitis in rats. A novel PAR2 antagonist (5-isoxazoyl-Cha-Ile-spiro[indene-1,4′-piperidine]; GB88) was evaluated for the blockade of intracellular calcium release in colonocytes and anti-inflammatory activity in acute (PAR2 agonist-induced) versus chronic [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] models of colitis in Wistar rats. Disease progression (disease activity index, weight loss, and mortality) and postmortem colonic histopathology …
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RJ Lohman, AJ Cotterell, J Suen, L Liu, AT Do… - Journal of Pharmacology and Experimental …, 2012