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-circuit 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.
Aikawa
N
N
The Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
Ohmori
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
D000930:Antidiarrheals; D001562:Benzimidazoles; D002147:Calmodulin; C052087:CGS 9343B; D000001:Calcimycin; D013779:Tetrodotoxin; D000109:Acetylcholine; D002118:Calcium