GABAA receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
GABAA receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts
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DOI：
10.1016/j.neuropharm.2008.06.013
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Moehler, Hanns
中科院分区：
文献类型：
--
作者：
Benke, Dietmar;Barberis, Andrea;Moehler, Hanns
几个世纪以来，缬草提取物一直被用来缓解不安和焦虑，尽管其体内作用机制尚不清楚。我们现在描述了 GABA(A) 受体上的一个特定结合位点，对缬草的常见成分戊酸和戊烯醇具有 nM 亲和力。两种药物均增强了多种重组 GABA(A) 受体对 GABA 的反应。重组受体β2或β3亚基（N265M）的点突变强烈降低了药物反应。在体内，戊酸和戊烯醇在野生型小鼠的高架十字迷宫和光/暗选择测试中发挥高效的抗焦虑活性。在β 3 (N265M) 点突变小鼠中，戊酸不具有抗焦虑活性。因此，表达含有 GABA(A) 受体的 β3 的神经元是缬草提取物抗焦虑作用的主要细胞底物。 (C) 2008 Elsevier Ltd. 保留所有权利。
Valerian extracts have been used for centuries to alleviate restlessness and anxiety albeit with unknown mechanism of action in vivo. We now describe a specific binding site on GABA(A) receptors with nM affinity for valerenic acid and valerenol, common constituents of valerian. Both agents enhanced the response to GABA at multiple types of recombinant GABA(A) receptors. A point mutation in the beta 2 or beta 3 subunit (N265M) of recombinant receptors strongly reduced the drug response. In vivo, valerenic acid and valerenol exerted anxiolytic activity with high potencies in the elevated plus maze and the light/dark choice test in wild type mice. In beta 3 (N265M) point-mutated mice the anxiolytic activity of valerenic acid was absent. Thus, neurons expressing beta 3 containing GABA(A) receptors are a major cellular substrate for the anxiolytic action of valerian extracts. (C) 2008 Elsevier Ltd. All rights reserved.