Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
2003 Dec 01;1408:1363-72. doi: 10.1038/sj.bjp.0705542.
Show Gene links
Show Anatomy links
Thymol, a constituent of thyme essential oil, is a positive allosteric modulator of human GABA(A) receptors and a homo-oligomeric GABA receptor from Drosophila melanogaster.
Priestley CM, Williamson EM, Wafford KA, Sattelle DB.
???displayArticle.abstract???
The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABAA and Drosophila melanogaster homomeric RDLac GABA receptors expressed in Xenopus laevis oocytes, voltage-clamped at -60 mV. The site of action of thymol was also investigated. Thymol, 1-100 microm, resulted in a dose-dependent potentiation of the EC20 GABA response in oocytes injected with either alpha1beta3gamma2s GABAA subunit cDNAs or the RDLac subunit RNA. At 100 microm thymol, current amplitudes in response to GABA were 416+/-72 and 715+/-85% of controls, respectively. On both receptors, thymol, 100 microm, elicited small currents in the absence of GABA. The EC50 for GABA at alpha1beta3gamma2s GABAA receptors was reduced by 50 microm thymol from 15+/-3 to 4+/-1 microm, and the Hill slope changed from 1.35+/-0.14 to 1.04+/-0.16; there was little effect on the maximum GABA response. Thymol (1-100 microm) potentiation of responses to EC20 GABA for alpha1beta1gamma2s, alpha6beta3gamma2s and alpha1beta3gamma2s human GABAA receptors was almost identical, arguing against actions at benzodiazepine or loreclezole sites. Neither flumazenil, 3-hydroxymethyl-beta-carboline (3-HMC), nor 5alpha-pregnane-3alpha, 20alpha-diol (5alpha-pregnanediol) affected thymol potentiation of the GABA response at alpha1beta3gamma2s receptors, providing evidence against actions at the benzodiazepine/beta-carboline or steroid sites. Thymol stimulated the agonist actions of pentobarbital and propofol on alpha1beta3gamma2s receptors, consistent with a mode of action distinct from that of either compound. These data suggest that thymol potentiates GABAA receptors through a previously unidentified binding site.
Aeschbach,
Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol.
1994, Pubmed
Aeschbach,
Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxytyrosol.
1994,
Pubmed Amin,
A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor.
1999,
Pubmed Aspinwall,
The interactions of hexachlorocyclohexane isomers with human gamma-aminobutyric acid(A) receptors expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase Barnard,
International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.
1998,
Pubmed Belelli,
Interaction of positive allosteric modulators with human and Drosophila recombinant GABA receptors expressed in Xenopus laevis oocytes.
1996,
Pubmed
,
Xenbase Belelli,
General anaesthetic action at transmitter-gated inhibitory amino acid receptors.
1999,
Pubmed Bloomquist,
Ion channels as targets for insecticides.
1996,
Pubmed Brown,
Functional cDNA libraries from Drosophila embryos.
1988,
Pubmed Changeux,
Allosteric receptors after 30 years.
1998,
Pubmed Cosentino,
In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils.
1999,
Pubmed Doliwa,
Effect of passive and iontophoretic skin pretreatments with terpenes on the in vitro skin transport of piroxicam.
2001,
Pubmed ffrench-Constant,
A single-amino acid substitution in a gamma-aminobutyric acid subtype A receptor locus is associated with cyclodiene insecticide resistance in Drosophila populations.
1993,
Pubmed Ffrench-Constant,
Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor locus.
1991,
Pubmed Franks,
Molecular and cellular mechanisms of general anaesthesia.
1994,
Pubmed Hadingham,
Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors.
1993,
Pubmed Hadingham,
Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors.
1993,
Pubmed
,
Xenbase Hadingham,
Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors.
1996,
Pubmed
,
Xenbase Hill-Venning,
Subunit-dependent interaction of the general anaesthetic etomidate with the gamma-aminobutyric acid type A receptor.
1997,
Pubmed
,
Xenbase Hosie,
Allosteric modulation of an expressed homo-oligomeric GABA-gated chloride channel of Drosophila melanogaster.
1996,
Pubmed
,
Xenbase Hosie,
Actions of the insecticide fipronil, on dieldrin-sensitive and- resistant GABA receptors of Drosophila melanogaster.
1995,
Pubmed
,
Xenbase Hosie,
Molecular biology of insect neuronal GABA receptors.
1997,
Pubmed Hosie,
Actions of picrodendrin antagonists on dieldrin-sensitive and -resistant Drosophila GABA receptors.
1996,
Pubmed
,
Xenbase Hummelbrunner,
Acute, sublethal, antifeedant, and synergistic effects of monoterpenoid essential oil compounds on the tobacco cutworm, Spodoptera litura (Lep., Noctuidae).
2001,
Pubmed Koenig,
Effect of free fatty acids on GABAA receptor ligand binding.
1992,
Pubmed Korpi,
Drug interactions at GABA(A) receptors.
2002,
Pubmed Lee,
Insecticidal activity of monoterpenoids to western corn rootworm (Coleoptera: Chrysomelidae), twospotted spider mite (Acari: Tetranychidae), and house fly (Diptera: Muscidae).
1997,
Pubmed Manabe,
Effects of essential oils on erythrocytes and hepatocytes from rats and dipalmitoyl phosphatidylcholine-liposomes.
1987,
Pubmed Mansour,
Botanical biocides. 4. Mosquitocidal activity of certain Thymus capitatus constituents.
2000,
Pubmed Mohammadi,
Structural requirements of phenol derivatives for direct activation of chloride currents via GABA(A) receptors.
2001,
Pubmed Moss,
Constructing inhibitory synapses.
2001,
Pubmed Peters,
Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids.
1988,
Pubmed Pistis,
Complementary regulation of anaesthetic activation of human (alpha6beta3gamma2L) and Drosophila (RDL) GABA receptors by a single amino acid residue.
1999,
Pubmed
,
Xenbase Rabow,
From ion currents to genomic analysis: recent advances in GABAA receptor research.
1995,
Pubmed Robertson,
Actions of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones.
1989,
Pubmed Sanna,
Characterization of the electrophysiological and pharmacological effects of 4-iodo-2,6-diisopropylphenol, a propofol analogue devoid of sedative-anaesthetic properties.
1999,
Pubmed
,
Xenbase Sattelle,
GABA receptors on the cell-body membrane of an identified insect motor neuron.
1988,
Pubmed Sieghart,
Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes.
1995,
Pubmed Sigel,
The effect of subunit composition of rat brain GABAA receptors on channel function.
1990,
Pubmed
,
Xenbase Singh,
Effect of active molluscicidal component of spices on different enzyme activities and biogenic amine levels in the nervous tissue of Lymnaea acuminata.
1999,
Pubmed Singh,
Amylase release from dissociated mouse pancreatic acinar cells stimulated by glucagon: effect of membrane stabilizers.
1980,
Pubmed Stevenson,
beta-Carboline gamma-aminobutyric acidA receptor inverse agonists modulate gamma-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site.
1995,
Pubmed
,
Xenbase Thomet,
A novel positive allosteric modulator of the GABA(A) receptor: the action of (+)-ROD188.
2000,
Pubmed
,
Xenbase Venturini,
In vitro antifungal activity of several antimicrobial compounds against Penicillium expansum.
2002,
Pubmed Wieland,
A single histidine in GABAA receptors is essential for benzodiazepine agonist binding.
1992,
Pubmed Woodward,
Effects of hexachlorocyclohexanes on gamma-aminobutyric acid receptors expressed in Xenopus oocytes by RNA from mammalian brain and retina.
1992,
Pubmed
,
Xenbase Yamakura,
Anesthetics and ion channels: molecular models and sites of action.
2001,
Pubmed
