Comparative effects of loperamide hydrochloride on prostaglandin E1-induced contraction in isolated fundus and ileum of guinea pigs.

The tension of isolated preparations of the fundus and the ileum of guinea pigs was measured isometrically to study the specific effect of loperamide hydrochloride on prostaglandin E1-induced contraction. Prostaglandin E1 caused concentration-dependent contraction in both the fundus and the ileum, and there was no significant difference between the fundus and the ileum. Loperamide hydrochloride inhibited prostaglandin E1-induced contraction in the fundus and the ileum. From the pD'2 value, loperamide hydrochloride caused greater inhibition of the contraction in the ileum than in the fundus. In a Ca(2+)-free solution containing 0.1 mM EGTA, prostaglandin E1-induced contraction in the ileum was almost eliminated, whereas 58% of the contraction in the fundus still remained. In Ca(2+)-free solution, loperamide hydrochloride and verapamil hydrochloride had no influence on prostaglandin E1-induced contraction, but markedly inhibited Ca(2+)-induced contraction. These results suggest that loperamide hydrochloride shows regional differences between gastrointestinal smooth muscles contracted by prostaglandin E1, and this may reflect one of the mechanisms in its antidiarrheal action through the suppression of peristalsis.