[The mode of action of bisacodyl on the smooth muscle of the small and the large intestine of the guinea pig].

Abstract

4,4'-Diacetoxy-diphenyl-(pyridyl-2)-methan (Bisacodyl, Dulcolax, 12--240 mug/ml) was shown to initiate dose-dependently contracile responses in the guinea pig isolated terminal ileum and taenia coli (a preparation of pure longitudinal muscle fibers). In contrast to muscle contractions induced by 1 mug/ml acetylcholine (ACh) and 1 mug/ml histamine, respectively bis-acodyl-induced contractile responses were antagonized neither by the anticholinergic agent atropine (6 mug/ml) nor by the antihistaminic compound pheniramine (6 mug/ml). On the other hand, bisacodyl inhibited contractile responses induced by ACh or histamine in a dose-dependent manner. The possibility that bisacodyl-induced contractions were due to a fall in cyclic 3,5-AMP level was excluded by estimation of endogenous cyclo-AMP. Since exogenous cyclic 3,5-AMP (which should possess calcium-antagonistic properties in smooth muscle) as well as verapamil (a calcium inhibitor) inhibited bisacodyl-induced contractions, a site of action on the calcium-dependent contractile system of the smooth muscle cell was discussed. Furthermore, bisacodyl should diminish the sensibility of the contractile system to other contractile compounds (ACh, histamine).