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Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons

文献类型:期刊论文

作者Ye, Zeng-You ; Lu, Yun-Gang ; Sun, Hao ; Cheng, Xin-Ping ; Xu, Tian-Le(徐天乐) ; Zhou, Jiang-Ning
刊名BRAIN RESEARCH
出版日期2008
卷号1239期号:pt 1页码:77-84
ISSN号0006-8993
关键词Antidepressant Fluoxetine-associated seizure Whole-cell patch-clamp Hippocampus Competitive inhibition Subtype-selectivity DORSAL-HORN NEURONS IN-VITRO SEIZURE ANTIDEPRESSANTS THERAPY BINDING SLICES NEUROSTEROIDS EXCITATION CHANNELS
通讯作者Zhou, JN (reprint author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China,zyye@mail.ustc.edu.cn
英文摘要Fluoxetine is a selective serotonin reuptake inhibitor widely used for treating depression. However, fluoxetine treatment may lead to seizures at higher doses, which underlying mechanism remains largely unknown. In this study, we examined the effects of fluoxetine on glycine receptor (GlyR) activity. Using the whole-cell patch-clamp recording method, we found that fluoxetine and its metabolite norfluoxetine inhibited glycine-induced currents in cultured rat hippocampal neurons. This inhibition was dose-dependent, and voltage-independent. Fluoxetine shifted the glycine concentration-response curve to the right without altering the maximal current. Both Lineweaver-Burk and Schild plots suggest competitive inhibition. The amount of fluoxetine inhibition significantly increased when homomeric GlyRs were selectively inhibited with picrotoxin. Moreover, fluoxetine inhibited the current mediated by heteromeric alpha 2 beta- but not homomeric alpha 2-GlyRs transiently expressed in HEK293T cells. These results suggest that fluoxetine is a competitive and subtype-selective GlyR inhibitor, which may explain its capacity to induce seizures. (C) 2008 Elsevier B.V. All rights reserved.
学科主题Neurosciences & Neurology
资助信息National Key Project for Basic Science of China[2006CB500705]; Natural Science Foundation of China[30530310]
收录类别SCI
语种英语
公开日期2012-07-23
源URL[http://ir.sibs.ac.cn/handle/331001/1692]  
专题上海神经科学研究所_神经所(总)
推荐引用方式
GB/T 7714
Ye, Zeng-You,Lu, Yun-Gang,Sun, Hao,et al. Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons[J]. BRAIN RESEARCH,2008,1239(pt 1):77-84.
APA Ye, Zeng-You,Lu, Yun-Gang,Sun, Hao,Cheng, Xin-Ping,Xu, Tian-Le,&Zhou, Jiang-Ning.(2008).Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons.BRAIN RESEARCH,1239(pt 1),77-84.
MLA Ye, Zeng-You,et al."Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons".BRAIN RESEARCH 1239.pt 1(2008):77-84.

入库方式: OAI收割

来源:上海神经科学研究所

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