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GABA A receptor modulation by terpenoids from Sideritis extracts
Author(s) -
Kessler Artur,
SahinNadeem Hilal,
Lummis Sarah C. R.,
Weigel Ingrid,
Pischetsrieder Monika,
Buettner Andrea,
Villmann Carmen
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300420
Subject(s) - terpene , receptor , terpenoid , gabaa receptor , chemistry , biochemistry , stereochemistry
Scope GABA A receptors are modulated by Sideritis extracts. The aim of this study was to identify single substances from Sideritis extracts responsible for GABA A 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 GABA A 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 GABA A 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 GABA A receptor function. Conclusion Comparing the chemical structures, the action of terpenes on GABA A 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.