Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery
文献类型：期刊论文
| 作者 | Wu, Zhong-shan2,3; Cheng, Hao2; Jiang, Yi2 ; Melcher, Karsten1; Xu, H. Eric1,2
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2015-08 |
| 卷号 | 36期号:8页码:895-907 |
| 关键词 | nAChR 5-HT3R structure biology subunit composition channel activation channel gating ion selectivity neurological disorders |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2015.66 |
| 文献子类 | Review |
| 英文摘要 | The nicotinic acetylcholine receptors (nAChRs) and the 5-HT3 receptors (5-HT(3)Rs) are cation-selective members of the pentameric ligand-gated ion channels (pLGICs), which are oligomeric protein assemblies that convert a chemical signal into an ion flux through postsynaptic membrane. They are critical components for synaptic transmission in the nervous system, and their dysfunction contributes to many neurological disorders. The diverse subunit compositions of pLGICs give rise to complex mechanisms of ligand recognition, channel gating, and ion-selective permeability, which have been demonstrated in numerous electrophysiological and molecular biological studies, and unraveled by progress in studying the structural biology of this protein family. In this review, we discuss recent insights into the structural and functional basis of two cation-selective pLGICs, the nAChR and the 5-HT3R, including their subunit compositions, ligand binding, and channel gating mechanisms. We also discuss their relevant pharmacology and drug discovery for treating various neurological disorders. Finally, we review a model of two alternative ion conducting pathways based on the latest 5-HT3A crystal structure. |
| WOS关键词 | LIGAND-BINDING DOMAIN ; POSITIVE ALLOSTERIC MODULATORS ; 5-HT3 RECEPTOR ANTAGONISTS ; NICOTINIC ACH RECEPTORS ; X-RAY-STRUCTURE ; NERVOUS-SYSTEM ; PHARMACOLOGICAL CHARACTERIZATION ; THERAPEUTIC TARGETS ; SMOKING-CESSATION ; CLINICAL-EFFICACY |
| 资助项目 | Jay and Betty Van Andel Foundation[00000000] ; Ministry of Science and Technology (China)[2012ZX09301001] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[2013CB910600] ; Ministry of Science and Technology (China)[XDB08020303] ; Ministry of Science and Technology (China)[2013ZX09507001] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5487139 |
| WOS记录号 | WOS:000358934000001 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276451]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Xu, H. Eric |
| 作者单位 | 1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, VARI SIMM Ctr,Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China; 3.Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Britton Chance Ctr Biomed Photon, Wuhan 430074, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wu, Zhong-shan,Cheng, Hao,Jiang, Yi,et al. Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery[J]. ACTA PHARMACOLOGICA SINICA,2015,36(8):895-907. |
| APA | Wu, Zhong-shan,Cheng, Hao,Jiang, Yi,Melcher, Karsten,&Xu, H. Eric.(2015).Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery.ACTA PHARMACOLOGICA SINICA,36(8),895-907. |
| MLA | Wu, Zhong-shan,et al."Ion channels gated by acetylcholine and serotonin: structures, biology, and drug discovery".ACTA PHARMACOLOGICA SINICA 36.8(2015):895-907. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。