A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats

作者：Zhao Juhui; Wang Jinhai^*; Dong Lei; Shi Hongyang; Wang Zongyan; Ding Hui; Shi Haitao; Lu Xiaolan

来源：European Journal of Pharmacology, 2011, 654(3): 289-294.

DOI：10.1016/j.ejphar.2010.12.032

• Acute restraint stress
• Paracellular permeability
• Protease inhibitor
• Visceral hypersensitivity

In the present study, we investigated the effects of camostat mesilate (CM), a synthetic protease inhibitor, on visceral sensitivity and paracellular permeability induced by the acute restraint stress. We also explored the possible mechanisms underlying these effects. The acute restraint stress was induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk of Sprague-Dawley rats for 2 h. Either CM (30, 100 and 300 mg/kg) or saline was intragastrically administrated to the rats 30 min before the acute restraint stress. Visceral perception was quantified as visceral motor response with an electromyography in a subset of rats. Paracellular permeability was determined in another subset of rats. We found that the visceral sensitivity and paracellular permeability were significantly reduced in the CM-treated rats. Moreover, the fecal protease activity was decreased in the CM-treated rats. The ZO-1 protein expression was markedly reduced by the stress treatment, but this decrease was suppressed by CM administration. Our data indicated that CM could efficiently inhibit visceral sensitivity and paracellular permeability induced by the acute restraint stress in rats. Therefore, CM might be an effective drug for the treatment of irritable bowel syndrome.

• 出版日期2011-3-11
• 单位西安交通大学