title: Direct effects of riluzole on 5-hydroxytryptamine (5-HT)3 receptor-activated ion currents in NCB-20 neuroblastoma cells.
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.
authors.affiliation: Department of Pharmacology, Medical Research Center, College of Medicine, The Catholic University of Korea, Korea.
authors.forename: Ki Jung
authors.initials: KJ
authors.lastname: Kim
authors.forename: Hyeong Seok
authors.initials: HS
authors.lastname: Cho
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Choi
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Jeun
authors.forename: Seong Yun
authors.initials: SY
authors.lastname: Kim
authors.forename: Ki-Wug
authors.initials: KW
authors.lastname: Sung
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials; D009447:Neuroblastoma / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D012701:Serotonin; D019782:Riluzole; D004298:Dopamine