Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening
文献类型：期刊论文
| 作者 | Song, MK; Liu, H ; Jiang, HL; Yue, JM; Hu, GY
|
| 刊名 | EUROPEAN JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2006-02-15 |
| 卷号 | 531期号:1-3页码:47-53 |
| 关键词 | 14-benzoyltalatisamine channel blocker delayed rectifier K+ channel drug discovery tetraethylammonium virtual screening |
| ISSN号 | 0014-2999 |
| DOI | 10.1016/j.ejphar.2005.12.029 |
| 文献子类 | Article |
| 英文摘要 | 14-Benzoyltalatisarnine is a potent and selective blocker of the delayed rectifier K+ channel found in a computational virtual screening Study. The compound was found to block the K+ channel from the extracellular side. However, it is unclear whether 14-benzoyltalatisamine shares the same block mechanism with tetraethylammonium (TEA). In order to elucidate how the hit compound found by the virtual screening interacts with the outer vestibule of the K+ channel, the effects of 14-berizoyltalatisamine and TEA oil the delayed rectifier K+ current of rat dissociated hippocampal neurons were compared using whole-cell voltage-clamp recording. External application of 14-benzoyltalatisamine and TEA reversibly inhibited the current with IC50 values of 10.1 +/- 2.2 mu M and 1.05 +/- 0.21 mM, respectively. 14-Benzoyltalatisamine exerted voltage-dependent inhibition, markedly accelerated the decay of the current, and caused a significant hyperpolarizing shift of the steady-state activation curve, whereas TEA caused voltage-independent inhibition, without affecting the kinetic parameters of the current. The blockade by 14-benzoyltalatisamine, but not by TEA, was significantly diminished in a high K+ (60 mM) external solution. The potency of 14-benzoyltalatisamine was markedly reduced in the presence of 15 mM TEA. The results suggest that 14-berizoyltalatisamine bind to the external pore entry ofthe delayed rectifier K+ channel with partial insertion into the selectivity filter, which is in conformity with that predicted by the molecular docking model in the virtual screening. (c) 2005 Elsevier B.V. All rights reserved. |
| WOS关键词 | OUTWARD POTASSIUM CURRENT ; GATED ION CHANNELS ; DRUG TARGETS ; NEURONS ; ENHANCEMENT ; DISCOVERY ; CA3 |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000235566200008 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273667]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Hu, GY |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, MK,Liu, H,Jiang, HL,et al. Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2006,531(1-3):47-53. |
| APA | Song, MK,Liu, H,Jiang, HL,Yue, JM,&Hu, GY.(2006).Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening.EUROPEAN JOURNAL OF PHARMACOLOGY,531(1-3),47-53. |
| MLA | Song, MK,et al."Electrophysiological characterization of 14-benzoyltalatisamine, a selective blocker of the delayed rectifier K+ channel found in virtual screening".EUROPEAN JOURNAL OF PHARMACOLOGY 531.1-3(2006):47-53. |
入库方式： OAI收割
来源：上海药物研究所
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