[Drug-induced anomalous contraction of gastrointestinal tract of mice with impaired c-kit function].
Drug-induced contraction of gastrointestinal tracts seems to depend upon the extent of their rhythmic contraction that is driven by the activity of gastrointestinal pacemaker cells. In BALB/c mice chronically administrated with a neutralizing anti-c-Kit monoclonal antibody (ACK2), rhythmic contraction of the gastrointestinal tract was impaired and contractile responses to drugs, including acetylcholine, prostaglandin F(2alpha), and bradykinin, were anomalously augmented. Histochemical analysis of the c-kit-positive cells in the gastrointestinal 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 Ca(2+)-dependent rhythmic Cl(-) current, the rhythmic current is supposed to be an origin of gastrointestinal pacemakers. The extent of anomaly in drug-induced contraction correlated with the extent of impairment in rhythmic contraction. The drug-induced anomalous contraction in the preparation from ACK2-treated animals, which is accompanied by the impaired rhythmic contraction, was mimicked when the gastrointestinal segments from control animals were superfused with a low temperature organ bath solution at 25 degrees C. These results suggest that rhythmic discharge of excitation of smooth muscle cells, which is triggered by rhythmic excitatory input from c-kit cells, regulates the extent of drug-induced contraction.
Tokutomi
Naofumi
N
Department of Cell and Biological Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Japan. tokutomi@gpo.kumamoto-u.ac.jp
Tokutomi
Yoshiko
Y
Nishi
Katsuhide
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019009:Proto-Oncogene Proteins c-kit