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, isometric muscle tension recordings and patch clamp techniques. Glivec (10 microM) converted action potential bursts into continuous firing without affecting their shape but at 50 microM abolished spontaneous action potentials. It had little effect on inward and outward currents at <10 microM, but inhibited them at >50 microM. 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.