Action of loperamide on neuronally mediated and Ca2+- or cAMP-mediated secretion in rat colon.

The action of loperamide on the ion secretion evoked in rat colon descendens by electric field stimulation of enteric neurons, on the Ca2+-dependent secretion due to carbachol, and on the cAMP-mediated secretion elicited by forskolin was studied. Loperamide blocked all three types of secretion, but about 10 times higher concentrations of the drug were necessary to block the secretion caused by forskolin than to block the secretion mediated neuronally or by Ca2+. All the effects of loperamide were mimicked by trifluoperazine, a calmodulin antagonist. Neither morphine nor the Ca2+ channel blocker, verapamil, mimicked the effects of loperamide on ion transport. Therefore it seems reasonable to conclude that the antisecretory action of loperamide in the rat colon is caused by a block of the calmodulin system.