Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate

ObjectiveTo investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Materials and Methods Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50m). Results Imatinib mesylate (1-10m), did not significantly affect slow waves recorded in the prostate of both age groups but at 50m, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P <0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35 and 41 of control, while the frequency was reduced to 15.7 at 1m (n = 7), 49.8 at 5m (n = 10), 46.2 at 10m (n = 7) and 53.1 at 50m (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15 and 3.3 at 1m (n = 6); 21.1 and 20.8 at 5m (n = 8); 58.4 and 8.8 at 10m (n = 11); 72.7 and 60 at 50m (n = 5). Conclusions A significant reduction in contractions but persistence of slow waves suggests imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib mesylate also significantly reduced contractions in the prostates of younger guinea pigs more than older ones, which is consistent with the notion that the younger guinea-pig prostate is more reliant on the tyrosine-dependent pacemaker ability of interstitial cells of Cajal-like prostatic interstitial cells.