中国科学院上海生命科学研究院神经科学研究所机构知识库
Advanced  
SIBS OpenIR  > 神经所(总)  > 期刊论文
Title: alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors
Author: Zhang, Xiao-Bing ; Sun, Guang-Chun ; Liu, Lu-Ying ; Yu, Fang ; Xu, Tian-Le(徐天乐)
Source: MOLECULAR PHARMACOLOGY
Issued Date: 2008
Volume: 73, Issue:4, Pages:1195-1202
Keyword: RAT HIPPOCAMPAL-NEURONS ; GATED ION CHANNELS ; MESSENGER-RNAS ; SPINAL-CORD ; IN-VITRO ; SUBUNIT ; MOUSE ; RESPONSES ; EXPRESSION ; ACTIVATION
Subject: Pharmacology & Pharmacy
Corresponding Author: Xu, TL (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,tlxu@ion.ac.cnu
English Abstract: In the mammalian cortex, alpha 2 subunit-containing glycine receptors (GlyRs) mediate tonic inhibition, but the precise functional role of this type of GlyRs is difficult to establish because of the lack of subtype-selective antagonist. In this study, we found that cyclothiazide (CTZ), an epileptogenic agent, potently inhibited GlyR-mediated current (I-Gly) in cultured rat hippocampal neurons. The inhibition was glycine concentration-dependent, suggesting a competitive mechanism. Note that GlyRs containing the alpha 2 but not alpha 1 or alpha 3 subunits, when being heterologously expressed in human embryonic kidney 293T cells, were inhibited by CTZ, indicating subunit specificity of CTZ action. In addition, the degree of CTZ inhibition on I-Gly in rat spinal neurons declined with time in culture, in parallel with a decline of alpha 2 subunit expression, which is known to occur during spinal cord development. Furthermore, site-directed mutagenesis indicates that a single-amino acid threonine at position 59 near the N terminus of the alpha 2 subunit confers the specificity of CTZ action. Thus, CTZ is a potent and selective inhibitor of alpha 2-GlyRs, and threonine at position 59 plays a critical role in the susceptibility of GlyR to CTZ inhibition.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1734
Appears in Collections:神经所(总)_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
Zhang-2008-alpha 2 subunit spec.pdf(457KB)----开放获取View Download

Recommended Citation:
Zhang, Xiao-Bing; Sun, Guang-Chun; Liu, Lu-Ying; Yu, Fang; Xu, Tian-Le.alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors,MOLECULAR PHARMACOLOGY,2008,73(4):1195-1202
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Zhang, Xiao-Bing]'s Articles
[Sun, Guang-Chun]'s Articles
[Liu, Lu-Ying]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Zhang, Xiao-Bing]‘s Articles
[Sun, Guang-Chun]‘s Articles
[Liu, Lu-Ying]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: Zhang-2008-alpha 2 subunit spec.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!