alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors

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	alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors
	Zhang, Xiao-Bing ; Sun, Guang-Chun ; Liu, Lu-Ying ; Yu, Fang ; Xu, Tian-Le(徐天乐)
刊名	MOLECULAR PHARMACOLOGY
	2008
卷号	73 期号:4 页码:1195-1202
关键词	RAT HIPPOCAMPAL-NEURONS GATED ION CHANNELS MESSENGER-RNAS SPINAL-CORD IN-VITRO SUBUNIT MOUSE RESPONSES EXPRESSION ACTIVATION
ISSN号	0026-895X
通讯作者	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
英文摘要	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.
学科主题	Pharmacology & Pharmacy
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1734]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Zhang, Xiao-Bing,Sun, Guang-Chun,Liu, Lu-Ying,et al. alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors[J]. MOLECULAR PHARMACOLOGY,2008,73(4):1195-1202.
APA	Zhang, Xiao-Bing,Sun, Guang-Chun,Liu, Lu-Ying,Yu, Fang,&Xu, Tian-Le.(2008).alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors.MOLECULAR PHARMACOLOGY,73(4),1195-1202.
MLA	Zhang, Xiao-Bing,et al."alpha 2 subunit specificity of cyclothiazide inhibition on glycine receptors".MOLECULAR PHARMACOLOGY 73.4(2008):1195-1202.