Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha 1-subunits

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	Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha 1-subunits
	Lu, Y-G ; Tang, Z-Q ; Ye, Z-Y ; Wang, H-T ; Huang, Y-N ; Zhou, K-Q ; Zhang, M. ; Xu, T-L ; Chen, L.
刊名	BRITISH JOURNAL OF PHARMACOLOGY
	2009
卷号	157 期号:8 页码:1514-1522
关键词	salicylate glycine receptor whole-cell patch-clamp transfection cell culture site-directed mutagenesis RAT INFERIOR COLLICULUS NONSTEROIDAL ANTIINFLAMMATORY DRUGS DORSAL-HORN NEURONS SODIUM-SALICYLATE POSTSYNAPTIC CURRENTS ALZHEIMERS-DISEASE KAPPA-B CHANNELS MODULATION RESPONSES
ISSN号	0007-1188
通讯作者	Chen, L (reprint author), Univ Sci & Technol China, Auditory Res Lab, Hefei 230027, Peoples R China,linchen@ustc.edu.cn
英文摘要	Background and purpose: Aspirin or its metabolite sodium salicylate is widely prescribed and has many side effects. Previous studies suggest that targeting neuronal receptors/ion channels is one of the pathways by which salicylate causes side effects in the nervous system. The present study aimed to investigate the functional action of salicylate on glycine receptors at a molecular level. Experimental approach: Whole-cell patch-clamp and site-directed mutagenesis were deployed to examine the effects of salicylate on the currents mediated by native glycine receptors in cultured neurones of rat inferior colliculus and by glycine receptors expressed in HEK293T cells. Key results: Salicylate effectively inhibited the maximal current mediated by native glycine receptors without altering the EC(50) and the Hill coefficient, demonstrating a non-competitive action of salicylate. Only when applied simultaneously with glycine and extracellularly, could salicylate produce this antagonism. In HEK293T cells transfected with either alpha 1-, alpha 2-, alpha 3-, alpha 1 beta-, alpha 2 beta- or alpha 3 beta-glycine receptors, salicylate only inhibited the current mediated by those receptors that contained the alpha 1-subunit. A single site mutation of I240V in the alpha 1-subunit abolished inhibition by salicylate. Conclusions and implications: Salicylate is a non-competitive antagonist specifically on glycine receptors containing alpha 1-subunits. This action critically involves the isoleucine-240 in the first transmembrane segment of the alpha 1-subunit. Our findings may increase our understanding of the receptors involved in the side effects of salicylate on the central nervous system, such as seizures and tinnitus.
学科主题	Pharmacology & Pharmacy
收录类别	SCI
资助信息	National Natural Science Foundation of China[30470560, 30730041]; National Basic Research Program of Chin[2007CB512306]; CAS Knowledge Innovation Project[KSCX1-YW-R-36]
语种	英语
公开日期	2012-07-13
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1649]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Lu, Y-G,Tang, Z-Q,Ye, Z-Y,et al. Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha 1-subunits[J]. BRITISH JOURNAL OF PHARMACOLOGY,2009,157(8):1514-1522.
APA	Lu, Y-G.,Tang, Z-Q.,Ye, Z-Y.,Wang, H-T.,Huang, Y-N.,...&Chen, L..(2009).Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha 1-subunits.BRITISH JOURNAL OF PHARMACOLOGY,157(8),1514-1522.
MLA	Lu, Y-G,et al."Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing alpha 1-subunits".BRITISH JOURNAL OF PHARMACOLOGY 157.8(2009):1514-1522.