Effect of cisapride on the isolated guinea pig gall bladder and common bile duct

Abstract

1. In this study, the effect of cisapride on the isolated guinea pig gall bladder (GB) and common bile duct (CBD) motility was investigated. 2. Cisapride, up to a certain concentration, produced an increase in tone of the GB (EC50 1.35 x 10-8 M) and the CBD (EC50 2.75 x 10-9 M), whereas, at concentrations higher than 3 x 10-5 M for the GB and 5 x 10-6 M for the CBD, it produced a transient increase in tone followed by a sustained decrease in tone or in the contraction amplitude or in both. 3. The cisapride-induced increase in tone was antagonized by atropine on both the GB and the CBD. 4. Cisapride up to 2 x 10-5 M for the GB and 3 x 10-6 M for the CBD did not modify, whereas, at concentrations higher than 2.8 x 10-5 M for the GB and 4 x 10-6 M for the CBD, it antagonized, noncompetitively, the concentration-response curve to exogenously applied acetylcholine. The IC50 values for cisapride on the EC50 of acetylcholine on the GB and the CBD were 9.4 x 10-5 M and 8.2 x 10-6 M, respectively. 5. In conclusion, on the guinea pig GB and CBD, low concentrations of cisapride produce a stimulating effect, probably of cholinergic origin, whereas higher concentrations produce a transient stimulating effect, probably of cholinergic origin, followed by a sustained relaxing effect, which may involve both cholinergic and noncholinergic pathways.