S64-5 Anomalous drug-induced contraction of gastrointestinal tract of mice with impaired c-kit function

• Published in: Journal of Pharmacological Sciences Vol. 91; no. suppl.1; p. 60
• Main Authors: Naofumi Tokutomi, Yoshiko Tokutomi, Katsuhide Nishi
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2003
• ISSN: 1347-8613

Drug-induced contraction of gastrointestinal (GI) tract seems to be balanced by the input and output of excitation among cell types involved. In BALB/c mice chronically administered with a neutralizing anti-c-kit monoclonal antibody (ACK2), rhythmic contraction of the GI tract was impaired and the contractile responses to drugs, including bradykinin, acetylcholine and prostaglandin F2α were anomalously augmented. Histochemical analysis in the GI tract revealed the decreased number of c-kit positive cells in the ACK2-treated animals, which lead to the impaired rhythmic contraction. Since the intestinal c-kit positive cells in primary culture developed Ca2+-dependent rhythmic Cl- current, the rhythmic current is supposed to be an origin of GI pacemakers. The extent of anomaly in the drug-induced contraction correlated with the extent of impairment in rhythmic contraction. The anomalous drug-induced contraction, which was accompanied by the impaired rhythmic contraction, was mimicked by the effects of superfusion with a low temperature organ bath solution at 25゜ C. These results suggest that rhythmic discharge of excitation of GI smooth muscle cells, which may be triggered by rhythmic electrical input from the c-kit positive cells, regulates the extent of drug-induced contraction.