Direct Effects of Riluzole on 5-Hydroxytryptamine (5-HT)3 Receptor–Activated Ion Currents in NCB-20 Neuroblastoma Cells
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概要
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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 μM, 5 s) produced a dose-dependent reduction in peak amplitudes and in the rise slope of the currents induced by 2 μM 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-[β-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.
著者
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Choi Se
Department Of Obstetrics And Gynecology College Of Medicine The Catholic University Of Korea
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Cho Hyeong
Department Of Pharmacology Medical Research Center College Of Medicine The Catholic University Of Ko
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Kim Ki
Deparment Of Obstetrics & Gynecology College Of Medicine Pusan National University
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Sung Ki-wug
Department Of Pharmacology Medical Research Center College Of Medicine The Catholic University Of Ko
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JEUN Seung
Department of Pharmacology, College of Medicine, The Catholic University of Korea
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KIM Seong
Department of Agricultural Chemistry, The University of Tokyo
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Sung Ki-Wug
Department of Pharmacology, Medical Research Center, College of Medicine, The Catholic University of Korea, Korea
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