Histamine release as the basis for morphine action on bile duct and sphincter of Oddi.

We have investigated the mechanism by which morphine contracts hog bile duct and sphincter of Oddi. Morphine contraction is antagonized by naloxone, competitively on the sphincter, noncompetitively on the bile duct. Diphenhydramine at low concentration (3.4 X 10(-6)M) also antagonizes both actions of morphine. Histamine has a very potent contracting action on the sphincter and bile duct and this is antagonized by diphenhydramine. Burimamide only weakly antagonizes the actions of morphine or histamine. Compound 48/80 causes a pronounced contraction of sphincter and bile duct following which morphine effects are greatly attenuated. These results suggest that morphine-induced contraction of the sphincter of Oddi and bile duct is mediated by a two step reaction involving interaction with a specific opiate receptor leading to the release of histamine which combines with an H1 receptor to produce the effect.