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ABSTRACT:Objective To investigate the role of PAR2 in the visceral sensitivity of IBS patients by observing the expression of rectal PAR2 in patients with irritable bowel syndrome and the effect of exogenous PAR2 on visceral sensitivity.Methods Based on Rome III criteria,16 patients with constipation predominant IBS (IBS-C),18 patients with diarrhea predominant IBS (IBS-D ),and 1 8 controls were selected from our hospital inpatient and outpatient departments. All the patients received colonoscopic examination and rectal mucosa biopsies. The expression of rectal mucosa PAR2 was observed by immunohistochemistry and Real-time fluorescence quantitative PCR.We studied the abdominal reactions by administering the PAR2 agonist in the rectal mucosa of rats to explore whether PAR2 is involved in visceral sensitivity.Results The results of PAR2 immunohistochemistry showed that PAR2 was mainly expressed in intestinal epithelial cells,especially in the villi;in addition,endothelial cells were also found positive.While the integral optical density (IA)of PAR2 expression did not significantly differ between IBS-D or IBS-C patients and controls according to the IPP image analysis.The PAR2 mRNA level in IBS-D or IBS-C patients was not significantly different from that of the control group by Real-time PCR analysis.There was no significant difference between the IBS-D and IBS-C groups.The EMG activity significantly increased in a volume-dependent manner during the rectal balloon expansion in the PAR2 agonist group.However,there was little EMG activity when the balloon was not dilated.The area under the curve in the PAR2 agonist group with 0 mL,0.4 mL and 0.6 mL of distension volume did not differ compared with that of the vehicle group.When the balloon volume increased to 0.8 mL,1.0 mL and 1.2 mL,the EMG activity was statistically significant (P<0.01)in the PAR2 agonist group compared with the control group.Conclusion PAR2 is highly expressed in the rectal mucosa of IBS patients.Administration of exogenous PAR2 agonist increases visceral sensitivity,suggesting that PAR2 is involved in visceral sensitivity.
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<p><b>OBJECTIVE</b>To observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.</p><p><b>METHODS</b>Sprague-Dawley rats were given 30, 100 or 300 mg/kg camostat mesilate (CM), a protease inhibitor, or saline intragastrically 30 min before acute restraint stress induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk for 2 h. Visceral perception of the rats was quantified as the visceral motor response with an electromyography, and the rectal mucosa and feces protease activity and spinal c-fos expression were measured.</p><p><b>RESULTS</b>CM dose-dependently reduced visceral sensitization elicited by rectal distension, but these doses did not completely inhibit stress-induced visceral sensitization. In normal rats, c-fos expression was found mainly in the superal spinal cord dorsal horn, and after the administration the CM, c-fos-positive cells decreased significantly in all dose groups (P<0.05). In 30 mg/kg CM group, fecal and rectal mucosal protease activity significantly decreased as compared with that in the stress group (P<0.05), and as CM dose increased to 100 and 300 mg/kg, the protease activity decreased even further (P<0.01).</p><p><b>CONCLUSION</b>The gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.</p>