Investigation of the effect of the c-kit inhibitor Glivec on isolated guinea-pig detrusor preparations

In order to assess the possible role of the c-kit positive cells in the bladder, the effects of c-kit tyrosine kinase inhibitor, Glivec®, on spontaneous excitation and ion channel activity in detrusor smooth muscles of the guinea-pig bladder were investigated using intracellular microelectrodes, iso...

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Bibliographic Details
Published in:Autonomic neuroscience 2004-09, Vol.115 (1), p.64-73
Main Authors: Kubota, Yasue, Kajioka, Shunichi, Biers, Suzanne M., Yokota, Etsuko, Kohri, Kenjiro, Brading, Alison F.
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Action Potentials - physiology
Animals
Benzamides
Biological and medical sciences
Bladder
c-kit
Fundamental and applied biological sciences. Psychology
Guinea Pigs
Imatinib Mesylate
Imatinib mesylate (Glivec)
In Vitro Techniques
Interstitial cells
Intracellular Signaling Peptides and Proteins - pharmacology
Male
Muscle Contraction - drug effects
Muscle Contraction - physiology
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - physiology
Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ
Piperazines - pharmacology
Proto-Oncogene Proteins c-kit - physiology
Pyrimidines - pharmacology
Smooth muscle
Urinary Bladder - drug effects
Urinary Bladder - physiology
Vertebrates: nervous system and sense organs
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Summary:In order to assess the possible role of the c-kit positive cells in the bladder, the effects of c-kit tyrosine kinase inhibitor, Glivec®, on spontaneous excitation and ion channel activity in detrusor smooth muscles of the guinea-pig bladder were investigated using intracellular microelectrodes, isometric muscle tension recordings and patch clamp techniques. Glivec (10 µM) converted action potential bursts into continuous firing without affecting their shape but at 50 µM abolished spontaneous action potentials. It had little effect on inward and outward currents at 50 µM. Glivec decreased the amplitude of spontaneous contractions dose dependently. These results suggest that c-kit positive cells may play a role in modulating spontaneous electrical and mechanical activities. Drugs inhibiting the c-kit receptor may provide a new approach for treating the overactive bladder.
ISSN:1566-0702
1872-7484
DOI:10.1016/j.autneu.2004.08.004