Effects of pinaverium bromide on the development of visceral hypersensitivity and expression of proteinase activated-receptor 2

Abstract

Objective To investigate the effect of pinaverium bromide on the development of visceral hypersensitivity and the expression of proteinase-activated-receptor 2(PAR2)in rats with water avoidance stress (WAS).Methods The Wistar rats were randomly divided into 3 groups with 12 each.The control group was submitted to sham-WAS and the group A1 was submitted to WAS.The rats in group A2 were submitted to WAS and received pinaverium bromide treatment (30 mg·kg~(-1)·d~(-1)).The stool pellets were counted during WAS and sham-WAS.The magnitude of visceromotor response (VMR) during colorectal distention was used to measure the changes of visceral hypersensitivity.The PAR2 expression was detected by immunofluorescence staining and Western blotting.Results Increased stool pellets were found in group A1 compared to the control group (8.10±2.75 vs.4.13±1.36,P<0.001).Pinaverium bromide treatment decreased stool pellets during WAS (5.87±1.78,P<0.001).The magnitude of VMR (60 mmHg) was higher in group Al compared to the control group (8.64±2.88 vs.3.80±1.04,P<0.001).Pinaverium bromidetreatment could decrease the magnitude of VMR effectively after WAS (6.09±0.77,P=0.02).The expression of PAR2 in group Al was significantly higher than that in the control group (rAU:0.70±0.06 vs.0.32±0.04;M:279.08±100.91 vs.77.16±10.74,P<0.001).The increased PAR2 expression induced by WAS could be inhibited by pinaverium bromide (rAU:0.53±0.06,IA:180.59±25.75,P<0.05).Conclusions Pinaverium bromide may decrease the expression of PAR2 and inhibit the development of visceral hypersensitivity in WAS rats. Key words: Visceral hypersensitivity; Pinaverium bromide; Proteinase activated-receptor 2