Imatinib blocks spontaneous mechanical activities in the adult mouse small intestine: Possible inhibition of c-Kit signaling

Naoki Shimojima, Toshio Nakaki, Yasuhide Morikawa, Ken Hoshino, Masaki Kitajima

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Interstitial cells of Cajal (ICCs) are postulated to serve as pacemakers that physiologically generate electrical slow waves in the gastrointestinal tract. Imatinib is a novel and potent inhibitor of c-Kit tyrosine kinase and a new therapeutic agent for gastrointestinal stromal tumors (GIST) which presumably arise from ICCs. The effects of imatinib on the basal rhythmic mechanical activities of small intestinal circular muscles were investigated in ring preparations of the gut. The small intestinal rings of BALB/c mice exhibited spontaneous contractile activity at a rate of 40.8 ± 4.9 contractions/min. Imatinib (1-81 μmol/l) dose-dependently abolished spontaneous contractile activity in the 9- to 27-μmol/l concentration range. Contraction was restored by washing imatinib out with a fresh buffer. High K+-induced contraction was not affected by imatinib, suggesting that the drug does not have nonspecific inhibitory actions on the smooth muscles. The small intestinal rings of adult W/Wv mice, which lack a functional c-Kit activity, exhibited only small and irregular spontaneous contractions. These results demonstrate that imatinib affects bowel contractions, and suggest that the c-Kit signaling of ICCs plays an essential role in the spontaneous movements in circular muscles of the mouse small intestine.

Original languageEnglish
Pages (from-to)95-99
Number of pages5
JournalPharmacology
Volume74
Issue number2
DOIs
Publication statusPublished - 2005 May 1

Keywords

  • Gastrointestinal motility
  • Interstitial cells of cajal
  • Pacemaker
  • Rhythmicity
  • Tyrosine kinase

ASJC Scopus subject areas

  • Pharmacology

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