Direct effects of riluzole on 5-hydroxytryptamine (5-HT)3 receptor-activated ion currents in NCB-20 neuroblastoma
Ki Jung Kim1, Hyeong Seok Cho, Se Joon Choi
1Department of Pharmacology, Medical Research Center, College of Medicine, The Catholic University of Korea, Korea.
Abstract:
The pharmacological action of riluzole, a drug that has been approved as a neuroprotective agent for the treatment of amyotrophic lateral sclerosis, has not yet been established. We examined the effects of riluzole on 5-hydroxytryptamine (5-HT)3) receptors in NCB-20 neuroblastoma cells using the whole-cell voltage clamp technique combined with a fast drug application method. Co-application of riluzole (1 - 300 microM, 5 s) produced a dose-dependent reduction in peak amplitudes and in the rise slope of the currents induced by 2 microM 5-HT. In addition, 5-HT3-mediated currents evoked by dopamine, a partial 5-HT3-receptor agonist, were inhibited by riluzole co-application. These inhibitory effects were clearly shown at low concentrations of 5-HT. The decay time constants of the receptor desensitization and deactivation were also significantly attenuated by riluzole. G-protein inhibitors (pertussis toxin and guanosine 5'-[beta-thio] diphosphate) did not completely block these inhibitory actions of riluzole. These results indicate that riluzole inhibits 5-HT3-induced ion currents directly by slowing channel activation in NCB-20 neuroblastoma cells.
