Nobuo Aikawa, Akira Karasawa and Kenji Ohmori
The Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.,
1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan
Abstract: 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 direct 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 presence of tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by inhibiting a tetrodotoxin-sensitive neuronal pathway and an intracellular Ca2+ pathway in epithelium.
Keywords: Zaldaride maleate, Calmodulin, Short-circuit current (Isc)