Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids
Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids
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DOI：
10.1016/j.ejphar.2004.10.026
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发表时间：
2004-12-03
影响因子：
5
通讯作者：
Burk, LA
中科院分区：
文献类型：
--
作者：
Hall, AC;Turcotte, CM;Burk, LA
研究了常见单萜醇和酮对非洲爪哇卵母细胞表达重组人γ-氨基丁酸A(α(A)；α(1)β(2)γ(2)S)和甘氨酸(α(1)异构体)受体的影响。10-300um：(+)-menthol>；(-)-menthol>；(-)-bomeo>；>；(-)-menthone=camphor对映体和香芹酮对映体与薄荷脑立体选择性地共同作用可增强GABA电流。相反，胡芦醇酮非对映异构体抑制GABA(A)受体电流，而甘氨酸电流仅被薄荷醇显著增强。鉴于(+)-薄荷醇的显著作用(例如，在100um时，GABA和甘氨酸EC20的反应分别增加496+/-113%和135+/-56%)，我们探索了(+)-薄荷醇的正向调制作用。(+)-薄荷醇使GABA和甘氨酸的EC50值分别从82.8+/-9.9和98.7+/-8.6降低到25.0+/-1.8um和75.7+/-9.4um，而对最大电流的影响可以忽略不计。这项研究揭示了薄荷醇作为抑制性配体门控通道的立体选择性调节剂的新的神经活性作用。(C)2004爱思唯尔B.V.保留所有权利。
Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABA(A); alpha(1)beta(2)gamma(2)s) and glycine (alpha(1) homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 muM: (+)-menthol>(-)-menthol>(-)-bomeo>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereo-selectively. By contrast, thujone diastereomers inhibited GABA(A) receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 muM, GABA and glycine EC20 responses increased by 496 +/- 113% and 135 +/- 56%, respectively). (+)-Menthol, 100 muM, reduced EC50 values for GABA and glycine from 82.8 +/- 9.9 to 25.0 +/- 1.8 muM, and from 98.7 +/- 8.6 to 75.7 +/- 9.4 muM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels. (C) 2004 Elsevier B.V. All rights reserved.