Reducing GABA receptors

被引:19
作者
Burt, DR [1 ]
机构
[1] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA
关键词
gamma-aminobutyric acid; knockdown; silencing; benzodiazepine; Anxiolytic; sedative; drug development;
D O I
10.1016/S0024-3205(03)00505-8
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A number of important drugs act on GABA(A) receptors, pentameric GABA-gated chloride channels assembled from among 19 known subunits. In trying to discover the roles in the brain of the subunits and their combinations, with the goal of developing more selective drugs, one tool has been to reduce expression of the subunits and examine the functional consequences. After briefly examining the properties of GABA(A) receptors, this review surveys the means available for receptor subunit reduction, and some of the observations to which their application has led. The methods discussed include radiation-induced deletion, gene knockout, knock-in mutations, antisense, ribozymes, RNA interference, dominant negative constructs, and transcriptional regulation, e.g., via decoy oligonucleotides. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:1741 / 1758
页数:18
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