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

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+]; 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 KCI induced [Ca2+], 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 x 10(-6) mol/L and 0.91 x 10(-6) mol/L, respectively. The IC50 values for inhibition of KCI induced contraction for the stress and control group were 8.13 x 10(-7) mol/L and 3.80 x 10(-7)mol/L, respectively. CONCLUSION: Increase in [Ca2+]; 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.