Molecular targets and mechanisms for ethanol action in glycine receptors.
Molecular targets and mechanisms for ethanol action in glycine receptors.
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DOI：
10.1016/j.pharmthera.2010.03.003
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发表时间：
2010-07
影响因子：
13.5
通讯作者：
Davies, Daryl L.
中科院分区：
文献类型：
--
作者：
Perkins, Daya I.;Trudell, James R.;Crawford, Daniel K.;Alkana, Ronald L.;Davies, Daryl L.
甘氨酸受体（GlyR）被认为是脊髓、脑干和已知对乙醇敏感的高级脑区域中神经元抑制的主要介质。越来越多的证据支持乙醇作用于GlyRs导致至少一部分行为效应的观点，并可能参与调节乙醇摄入量。二十多年来，GlyR作为乙醇作用的靶标在分子水平上被研究。尽管在了解乙醇在体内和体外的作用方面取得了进展，但乙醇在配体门控离子通道中的确切分子位点和作用机制，特别是在GlyR中，现在才开始被理解。本综述的重点是在我们的知识的进展，通过使用分子生物学，压力拮抗，电生理学和分子建模策略在过去的二十年来探测，识别和建模的初始分子位点和乙醇的作用机制在GlyRs。GlyR的分子靶点涵盖了全球范围，包括胞内，跨膜和胞外结构域。后者近年来受到越来越多的关注。最近的分子模型的乙醇作用的GlyRs及其影响，我们的理解可能的乙醇作用机制和药物开发的新目标GlyRs的网站进行了讨论。
Glycine receptors (GlyRs) are recognized as the primary mediators of neuronal inhibition in the spinal cord, brain stem and higher brain regions known to be sensitive to ethanol. Building evidence supports the notion that ethanol acting on GlyRs causes at least a subset of its behavioral effects and may be involved in modulating ethanol intake. For over two decades, GlyRs have been studied at the molecular level as targets for ethanol action. Despite the advances in understanding the effects of ethanol in vivo and in vitro, the precise molecular sites and mechanisms of action for ethanol in ligand-gated ion channels in general, and in GlyRs specifically, are just now starting to become understood. The present review focuses on advances in our knowledge produced by using molecular biology, pressure antagonism, electrophysiology and molecular modeling strategies over the last two decades to probe, identify and model the initial molecular sites and mechanisms of ethanol action in GlyRs. The molecular targets on the GlyR are covered on a global perspective, which includes the intracellular, transmembrane and extracellular domains. The latter has received increasing attention in recent years. Recent molecular models of the sites of ethanol action in GlyRs and their implications to our understanding of possible mechanism of ethanol action and novel targets for drug development in GlyRs are discussed.
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DOI：
10.1093/protein/15.6.443
发表时间：
2002-06-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Bertaccini, E;Trudell, JR
通讯作者：
Trudell, JR
影响因子：
5.6
作者：
BLABER, M;BAASE, WA;MATTHEWS, BW
通讯作者：
MATTHEWS, BW
影响因子：
4.7
作者：
Asatryan, Liana;Popova, Maya;Davies, Daryl L.
通讯作者：
Davies, Daryl L.
DOI：
10.1111/j.1530-0277.1992.tb00629.x
发表时间：
1992-02-01
影响因子：
3.2
作者：
ALKANA, RL;FINN, DA;SYAPIN, PJ
通讯作者：
SYAPIN, PJ
影响因子：
3.3
作者：
ARAKI, T;YAMANO, M;TOHYAMA, M
通讯作者：
TOHYAMA, M