Effect of pinaverium bromide on electrical and mechanical activity of smooth muscle cells.

Abstract

Pinaverium bromide exerts antagonistic effects on the contractions induced by BaCl2 in intestinal smooth muscle. We have therefore investigated its effects on the electrical and mechanical activity and on the 45Ca exchange of guinea-pig taenia coli and ileum. In the concentration range 10−7 to 10−5 M this drug does not exert an effect on the resting potential of either preparation. At 10−6 M no effects could be observed on the spontaneous electrical activity in taenia coli. However, in the ileum the frequency of the action potentials, as well as their amplitude and maximum rate of rise and of repolarization were significantly reduced, causing inhibitory effects on the concomitant mechanical responses. This effect is more pronounced at 10−5 M, and in some tissues the spontaneous activity is completely abolished. Similar effects have been observed in taenia coli at this concentration of pinaverium bromide. The contractions induced by K-depolarization and by 10−5 M carbachol are inhibited in both preparations in a dose-dependent way. Also the contraction induced by carbachol in Ca free solution, as well as the restoration of that contraction by exposing the tissues to Ca containing solutions are reduced in the presence of 10−5 M pinaverium bromide. Pinaverium also inhibits the stimulation of the 45Ca efflux induced by K-depolarization and by stimulation with 10−5 M carbachol. In rabbit ear artery it was found that the contraction induced by noradrenaline is much less sensitive to pinaverium bromide than that induced by depolarization. It was also observed that this substance does not significantly affect the noradrenaline induced contraction in Ca free solution, neither does it prevent the restoration of that contraction by exposure of the tissue to Ca containing solutions. These effects are similar to those observed with other Caentry blocking agents, and therefore suggest that pinaverium bromide mainly acts by blocking voltage-dependent Ca-channels.