Basic Research
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 15, 2003; 9(3): 557-561
Published online Mar 15, 2003. doi: 10.3748/wjg.v9.i3.557
Effect of pinaverium bromide on stress-induced colonic smooth muscle contractility disorder in rats
Yun Dai, Jian-Xiang Liu, Jun-Xia Li, Yun-Feng Xu
Yun Dai, Jian-Xiang Liu, Jun -Xia Li, Department of Gastroenterology, First Hospital of Peking University, Beijing 100034, China
Yun-Feng Xu, The Center Laboratory, First Hospital of Peking University, Beijing 100034, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Yun Dai, P.O. Box 97-242 Beijing 100016, China. caolanzi@263.net
Telephone: +86-10-66171122-2301
Received: September 14, 2002
Revised: October 10, 2002
Accepted: October 18, 2002
Published online: March 15, 2003
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 [Ca2+]i was measured in cell suspension using the Ca2+ 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 [Ca2+]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 [Ca2+]i increment was observed at 10-6 mol/L. The IC50 values for inhibition of ACh induced contraction for the stress and control group were 1.66 × 10-6 mol/L and 0.91 × 10-6 mol/L, respectively. The IC50 values for inhibition of KCl induced contraction for the stress and control group were 8.13 × 10-7 mol/L and 3.80 × 10-7 mol/L, respectively.

CONCLUSION: Increase in [Ca2+]i of smooth muscle cells is directly related to the generation of contraction force in colon. L-type Ca2+ channels represent the main route of Ca2+ 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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