An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl- of cultured rat hippocampal neurons via GABAc receptors
An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl- of cultured rat hippocampal neurons via GABAc receptors
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DOI：
10.1016/s0304-3940(01)02201-7
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发表时间：
2001-10-19
影响因子：
2.5
通讯作者：
Inagaki, C
中科院分区：
文献类型：
--
作者：
Irie, T;Miyamoto, E;Inagaki, C
用原代培养的大鼠海马神经元研究抗焦虑药和厚朴酚衍生物二氢和厚朴酚-B（DHH-B）[3 '-（2-丙烯基）-5-丙基-（1，1'-联苯）-2，4 '-二酚]对氨诱导的细胞内Cl-浓度（[Cl-]（i））增加的影响。DHH-B（1-100 ng/ml），而不是和厚朴酚的无活性异构体厚朴酚（100 ng/ml），剂量依赖性地抑制氨诱导的[Cl-]（i）的增加，而对照[Cl-]（i）没有任何变化。DHH-B的这种作用被γ-氨基丁酸A（GABA（A））和GABA（C）Cl-通道阻断剂100 μ M印防己毒素和GABA（C）受体阻断剂10 μ M（1，2，5，6-四氢吡啶-4-基）甲基次膦酸阻断，但不被GABA（A）受体阻断剂10 μ M荷包牡丹碱阻断。此外，GABA（C）受体激动剂200 μ M顺式-4-氨基巴豆酸，而不是GABAA受体激动剂10 μ M蝇蕈醇，模拟DHH-B的作用。因此，DHH-B似乎通过GABA（C）受体刺激保护神经元免受氨诱导的[Cl-]（i）增加。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
The effects of an anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B) [3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)2,4'-diaol], on ammonia-induced increases in the intracellular Cl- concentration ([Cl-](i)) were examined using primary cultured rat hippocampal neurons. DHH-B (1-100 ng/ml), but not an inactive isomer of honokiol, magnolol (100 ng/ml), dose-dependently inhibited the ammonia-induced increases in [Cl-](i) without any changes in the control [Cl-](i). Such an effect of DHH-B was blocked by a gamma-aminobutylic acid A (GABA(A)) and GABA(C) Cl- channel blocker, 100 muM picrotoxin, and a GABA(C) receptor blocker, 10 muM (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, but not by a GABA(A) receptor blocker, 10 muM bicuculline. Further, a GABA(C) receptor agonist, 200 muM cis-4-aminocrotonic acid, but not a GABAA receptor agonist, 10 muM muscimol, mimicked the effect of DHH-B. Thus, DHH-B appears to protect neurons from the ammonia-induced increases in [Cl-](i) through GABA(C) receptor stimulation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.