title: A protease inhibitor against acute stress-induced visceral hypersensitivity and paracellular permeability in rats.
abstract: 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 2h. Either CM (30, 100 and 300mg/kg) or saline was intragastrically administrated to the rats 30min 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.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.
authors.forename: Juhui
authors.initials: J
authors.lastname: Zhao
authors.forename: Jinhai
authors.initials: J
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.forename: Zongyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Haitao
authors.initials: H
authors.lastname: Shi
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000601:surgery; D012149:Restraint, Physical / Q000009:adverse effects; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D011480:Protease Inhibitors; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein