GABAA receptor modulation by terpenoids from Sideritis extracts
Article first published online: 24 NOV 2013
© 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Molecular Nutrition & Food Research
Volume 58, Issue 4, pages 851–862, April 2014
How to Cite
Kessler, A., Sahin-Nadeem, H., Lummis, S. C. R., Weigel, I., Pischetsrieder, M., Buettner, A. and Villmann, C. (2014), GABAA receptor modulation by terpenoids from Sideritis extracts. Mol. Nutr. Food Res., 58: 851–862. doi: 10.1002/mnfr.201300420
- Issue published online: 1 APR 2014
- Article first published online: 24 NOV 2013
- Manuscript Accepted: 15 SEP 2013
- Manuscript Revised: 12 SEP 2013
- Manuscript Received: 10 JUN 2013
- GABAA receptor;
- Patch clamp recordings;
- Two-electrode voltage clamp recordings;
- Volatile odorants
GABAA receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABAA receptor modulation.
Methods and results
Single volatile substances identified by GC have been tested in two expression systems, Xenopus oocytes and human embryonic kidney cells. Some of these substances, especially carvacrol, were highly potent on GABAA receptors composed of α1β2 and α1β2γ2 subunits. All effects measured were independent from the presence of the γ2 subunit. As Sideritis extracts contain a high amount of terpenes, 13 terpenes with similar structure elements were tested in the same way. Following a prescreening on α1β2 GABAA receptors, a high-throughput method was used for identification of the most effective terpenoid substances on GABA-affinity of α1β2γ2 receptors expressed in transfected cell lines. Isopulegol, pinocarveol, verbenol, and myrtenol were the most potent modifiers of GABAA receptor function.
Comparing the chemical structures, the action of terpenes on GABAA receptors is most probably due to the presence of hydroxyl groups and a bicyclic character of the substances tested. We propose an allosteric modulation independent from the γ2 subunit and similar to the action of alcohols and anesthetics.