title: GABA(A) receptor modulation by terpenoids from Sideritis extracts.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemistry and Pharmacy, Food Chemistry Division, University of Erlangen-Nuernberg, Erlangen, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Kessler
authors.forename: Hilal
authors.initials: H
authors.lastname: Sahin-Nadeem
authors.forename: Sarah C R
authors.initials: SC
authors.lastname: Lummis
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weigel
authors.forename: Monika
authors.initials: M
authors.lastname: Pischetsrieder
authors.forename: Andrea
authors.initials: A
authors.lastname: Buettner
authors.forename: Carmen
authors.initials: C
authors.lastname: Villmann
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D057809:HEK293 Cells / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry*; D011963:Receptors, GABA-A / Q000378:metabolism*; D031365:Sideritis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D010936:Plant Extracts; D011963:Receptors, GABA-A; D013729:Terpenes
keywords: GABAA receptor; Patch clamp recordings; Terpene; Two-electrode voltage clamp recordings; Volatile odorants