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. 2003 Mar;9(3):557-61.
doi: 10.3748/wjg.v9.i3.557.

Effect of pinaverium bromide on stress-induced colonic smooth muscle contractility disorder in rats

Yun Dai  1 , Jian-Xiang Liu, Jun-Xia Li, Yun-Feng Xu
Affiliations

Effect of pinaverium bromide on stress-induced colonic smooth muscle contractility disorder in rats

Yun Dai et al. World J Gastroenterol. 2003 Mar.

Abstract

Aim: To investigate the effect of pinaverium bromide, a L-type calcium channel blocker with selectivity for the gastrointestinal tract on contractile activity of colonic circular smooth muscle in normal or cold-restraint stressed rats and its possible mechanism.

Methods: Cold-restraint stress was conducted on rats to increase fecal pellets output. Each isolated colonic circular muscle strip was suspended in a tissue chamber containing warm oxygenated Tyrode-Ringer solution. The contractile response to ACh or KCl was measured isometrically on ink-writing recorder. Incubated muscle in different concentrations of pinaverium and the effects of pinaverium were investigated on ACh or KCl-induced contraction. Colon smooth muscle cells were cultured from rats and (Ca(2+))(i) was measured in cell suspension using the Ca(2+) fluorescent dye fura-2/AM.

Results: During stress, rats fecal pellet output increased 61 % (P<0.01). Stimulated with ACh or KCl, the muscle contractility was higher in stress than that in control. Pinaverium inhibited the increment of (Ca(2+))(i) and the muscle contraction in response to ACh or KCl in a dose dependent manner. A significant inhibition of pinaverium to ACh or KCl induced (Ca(2+))(i) increment was observed at 10(-6) mol/L. The IC(50) values for inhibition of ACh induced contraction for the stress and control group were 1.66X10(-6) mol/L and 0.91X10(-6) mol/L, respectively. The IC(50) values for inhibition of KCl induced contraction for the stress and control group were 8.13X10(-7) mol/L and 3.80X10(-7) mol/L, respectively.

Conclusion: Increase in (Ca(2+))(i) of smooth muscle cells is directly related to the generation of contraction force in colon. L-type Ca(2+) channels represent the main route of Ca(2+) entry. Pinaverium inhibits the calcium influx through L-type channels; decreases the contractile response to many kinds of agonists and regulates the stress-induced colon hypermotility.

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Figures

Figure 1
Figure 1
Effect of pinaverium on ACh-induced colonic circu-lar muscle contraction. aP < 0.05, vs control.
Figure 2
Figure 2
Effect of pinaverium on KCl-induced colonic circular muscle contraction. aP < 0.05, vs control.
Figure 3
Figure 3
Effect of ACh and KCl on [Ca2+]i and contraction of colonic smooth muscle.
See this image and copyright information in PMC

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