Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects
文献类型：期刊论文
| 作者 | Chen, Xue-Qin; Zhang, Jing; Neumeyer, John L.; Jin, Guo-Zhang ; Hu, Guo-Yuan; Zhang, Ao; Zhen, Xuechu
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| 刊名 | PLOS ONE
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| 出版日期 | 2009-06-05 |
| 卷号 | 4期号:6 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0005811 |
| 文献子类 | Article |
| 英文摘要 | (+/-) SKF83959, like many other arylbenzazepines, elicits powerful neuroprotection in vitro and in vivo. The neuroprotective action of the compound was found to partially depend on its D-1-like dopamine receptor agonistic activity. The precise mechanism for the (+/-) SKF83959-mediated neuroprotection remains elusive. We report here that (+/-) SKF83959 is a potent blocker for delayed rectifier K+ channel. (+/-) SKF83959 inhibited the delayed rectifier K+ current (I-K) dose-dependently in rat hippocampal neurons. The IC50 value for inhibition of I-K was 41.9 +/- 2.3 mu M (Hill coefficient = 1.81 +/- 0.13, n = 6), whereas that for inhibition of I-A was 307.9 +/- 38.5 mu M (Hill coefficient = 1.37 +/- 0.08, n = 6). Thus, (+/-) SKF83959 is 7.3-fold more potent in suppressing I-K than I-A. Moreover, the inhibition of I-K by (+/-) SKF83959 was voltage-dependent and not related to dopamine receptors. The rapidly onset of inhibition and recovery suggests that the inhibition resulted from a direct interaction of (+/-) SKF83959 with the K+ channel. The intracellular application of (+/-) SKF83959 had no effects of on I-K, indicating that the compound most likely acts at the outer mouth of the pore of K+ channel. We also tested the enantiomers of (+/-) SKF83959, R-(+) SKF83959 (MCL-201), and S-(-) SKF83959 (MCL-202), as well as SKF38393; all these compounds inhibited IK. However, (+/-) SKF83959, at either 0.1 or 1 mM, exhibited the strongest inhibition on the currents among all tested drug. The present findings not only revealed a new potent blocker of I-K, but also provided a novel mechanism for the neuroprotective action of arylbenzazepines such as (+/-) SKF83959. |
| 资助项目 | NIDA NIH HHS[R01 DA014251] ; NIDA NIH HHS[DA-14251] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000266717200007 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279212]  |
| 专题 | 药物化学研究室 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 药理学第二研究室 |
| 通讯作者 | Chen, Xue-Qin |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 2, State Key Lab Drug Res, Shanghai 200031, Peoples R China. |
| 推荐引用方式 GB/T 7714 | Chen, Xue-Qin,Zhang, Jing,Neumeyer, John L.,et al. Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects[J]. PLOS ONE,2009,4(6). |
| APA | Chen, Xue-Qin.,Zhang, Jing.,Neumeyer, John L..,Jin, Guo-Zhang.,Hu, Guo-Yuan.,...&Zhen, Xuechu.(2009).Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects.PLOS ONE,4(6). |
| MLA | Chen, Xue-Qin,et al."Arylbenzazepines Are Potent Modulators for the Delayed Rectifier K+ Channel: A Potential Mechanism for Their Neuroprotective Effects".PLOS ONE 4.6(2009). |
入库方式： OAI收割
来源：上海药物研究所
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