The Effects of the c-kit Blocker Glivec on the Contractile Response of Urinary Bladder

Objectives To investigate the effects of imatinib (Glivec) on the urinary bladder contraction and excitation induced by neurostimulation, therefore to clarify the relationships between the bladder interstitial cell of Cajal (ICC) and the neural signals. Methods In in vivo experiments, pelvic nerves of rats were stimulated by square-wave pulses. The contractile response was recorded before and 40 min after the administration of medications (atropine, Glivec, and ketotifen). In in vitro experiments, the bladder contractile response induced by acetylcholine with or without Glivec was evaluated. The space relationship between ICC and neural fibers were observed with double-labeled fluorescence using primary antibodies (anti-c-kit and anti-vesicular acetylcholine transferase) and secondary fluorescent antibodies (Alexa 488 and Alexa 594; Molecular Probes, Eugene, OR). Results Atropine and Glivec could significantly inhibit the bladder contractile response induced by the electrical stimulation in a dose-dependent manner, while ketotifen did not obviously affect bladder contractile response. In in vitro experiments, Glivec did not affect acetylcholine-induced bladder contractile response. The location of ICC in close proximity to cholinergic nerve fibers was confirmed by double-labeled fluorescence. Conclusions Bladder ICC play an important role as intermediaries in the transmission of cholinergic signals from nerve to smooth muscle cells.