Effects of zaldaride maleate, an antidiarrheal compound, on intracellular Ca2+-mediated short-circuit current response in the rat colonic mucosa

The effect of zaldaride maleate (ZAL) on intracellular Ca2+-mediated short- curcuit current (Isc) response in rat colonic mucosa was investigated. The Isc response to acetylcholine was partially reduced by the neuronal blocker tetrodotoxin. The tetrodotoxin-sensitive Isc response to acetylcholine was inhibited by ZAL. The tetrodotoxin-insensitive effect, which indicates dir ect stimulation of acetylcholine in colonic mucosa, was not affected by ZAL . The Isc response to the Ca2+ ionophore A23187 was reduced by ZAL in the p resence of tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by inhibiting a tetrodotoxin-sensitive neuronal pathway and an i ntracellular Ca2+ pathway in epithelium.