Effects of imatinib mesylate on spontaneous electrical and mechanical activity in smooth muscle of the guinea-pig stomach
Article first published online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Special Issue: Special Issue: Neuropharmacology of Addiction
Volume 154, Issue 2, pages 451–459, May 2008
How to Cite
Hashitani, H., Hayase, M. and Suzuki, H. (2008), Effects of imatinib mesylate on spontaneous electrical and mechanical activity in smooth muscle of the guinea-pig stomach. British Journal of Pharmacology, 154: 451–459. doi: 10.1038/bjp.2008.91
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received September 11, 2007, Revised December 20, 2007, Accepted February 13, 2008)
- imatinib mesylate;
- interstitial cells of Cajal;
- smooth muscle;
Background and purpose:
Effects of imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, on spontaneous activity of interstitial cells of Cajal (ICC) and smooth muscles in the stomach were investigated.
Effects of imatinib on spontaneous electrical and mechanical activity were investigated by measuring changes in the membrane potential and tension recorded from smooth muscles of the guinea-pig stomach. Its effects on spontaneous changes in intracellular concentration of Ca2+ ([Ca2+]i) (Ca2+ transients) were also examined in fura-2-loaded preparations.
Imatinib (1–10 μM) suppressed spontaneous contractions and Ca2+ transients. Simultaneous recordings of electrical and mechanical activity demonstrated that imatinib (1 μM) reduced the amplitude of spontaneous contractions without suppressing corresponding slow waves. In the presence of nifedipine (1 μM), imatinib (10 μM) reduced the duration of slow waves and follower potentials in the antrum and accelerated their generation, but had little affect on their amplitude. In contrast, imatinib reduced the amplitude of antral slow potentials and slow waves in the corpus.
Conclusions and implications:
Imatinib may suppress spontaneous contractions of gastric smooth muscles by inhibiting pathways that increase [Ca2+]i in smooth muscles rather than by specifically inhibiting the activity of ICC. A high concentration of imatinib (10 μM) reduced the duration of slow waves or follower potentials in the antrum, which reflect activity of ICC distributed in the myenteric layers (ICC-MY), and suppressed antral slow potentials or corporal slow waves, which reflect activity of ICC within the muscle bundles (ICC-IM), presumably by inhibiting intracellular Ca2+ handling.
British Journal of Pharmacology (2008) 154, 451–459; doi:10.1038/bjp.2008.91; published online 14 April 2008