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
2000 Feb 01;1294:731-43. doi: 10.1038/sj.bjp.0703087.
Show Gene links
Show Anatomy links
The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations.
Krasowski MD
,
Harrison NL
.
???displayArticle.abstract???
The actions of 13 general anaesthetics (diethyl ether, enflurane, isoflurane, methoxyflurane, sevoflurane, chloral hydrate, trifluoroethanol, tribromoethanol, tert-butanol, chloretone, brometone, trichloroethylene, and alpha-chloralose) were studied on agonist-activated Cl(-) currents at human GABA(A) alpha(2)beta(1), glycine alpha(1), and GABA(C) rho(1) receptors expressed in human embryonic kidney 293 cells. All 13 anaesthetics enhanced responses to submaximal (EC(20)) concentrations of agonist at GABA(A) and glycine receptors, except alpha-chloralose, which did not enhance responses at the glycine alpha(1) receptor. None of the anaesthetics studied potentiated GABA responses at the GABA(C) rho(1) receptor. Potentiation of submaximal agonist currents by the anaesthetics was studied at GABA(A) and glycine receptors harbouring mutations in putative transmembrane domains 2 and 3 within GABA(A) alpha(2), beta(1), or glycine alpha(1) receptor subunits: GABA(A) alpha(2)(S270I)beta(1), alpha(2)(A291W)beta(1), alpha(2)beta(1)(S265I), and alpha(2)beta(1)(M286W); glycine alpha(1)(S267I) and alpha(1)(A288W). For all anaesthetics studied except alpha-chloralose, at least one of the mutations above abolished drug potentiation of agonist responses at GABA(A) and glycine receptors. alpha-Chloralose produced efficacious direct activation of the GABA(A) alpha(2)beta(1) receptor (a 'GABA-mimetic' effect). The other 12 anaesthetics produced minimal or no direct activation of GABA(A) and glycine receptors. A non-anaesthetic isomer of alpha-chloralose, beta-chloralose, was inactive at GABA(A) and glycine receptors and did not antagonize the actions of alpha-chloralose at GABA(A) receptors. The implications of these findings for the molecular mechanisms of action of general anaesthetics at GABA(A) and glycine receptors are discussed.
Adodra,
Potentiation, activation and blockade of GABAA receptors of clonal murine hypothalamic GT1-7 neurones by propofol.
1995, Pubmed
Adodra,
Potentiation, activation and blockade of GABAA receptors of clonal murine hypothalamic GT1-7 neurones by propofol.
1995,
Pubmed
Allott,
Variation with temperature of the solubilities of inhaled anaesthetics in water, oil and biological media.
1973,
Pubmed
Banks,
Dual actions of volatile anesthetics on GABA(A) IPSCs: dissociation of blocking and prolonging effects.
1999,
Pubmed
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,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997,
Pubmed
,
Xenbase
Chang,
Stoichiometry of a recombinant GABAA receptor.
1996,
Pubmed
,
Xenbase
Cutting,
Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: a GABA receptor subunit highly expressed in the retina.
1991,
Pubmed
,
Xenbase
Dildy-Mayfield,
Actions of long chain alcohols on GABAA and glutamate receptors: relation to in vivo effects.
1996,
Pubmed
,
Xenbase
Downes,
Contrasting effects of anesthetics in tadpole bioassays.
1996,
Pubmed
Downie,
Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Eckenhoff,
Molecular interactions between inhaled anesthetics and proteins.
1997,
Pubmed
Eger,
Minimum alveolar anesthetic concentration of fluorinated alkanols in rats: relevance to theories of narcosis.
1999,
Pubmed
Eger,
Minimum alveolar anesthetic concentration: a standard of anesthetic potency.
1965,
Pubmed
Farrar,
Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer.
1999,
Pubmed
Franks,
Temperature dependence of the potency of volatile general anesthetics: implications for in vitro experiments.
1996,
Pubmed
Franks,
Selective actions of volatile general anaesthetics at molecular and cellular levels.
1993,
Pubmed
Franks,
Molecular and cellular mechanisms of general anaesthesia.
1994,
Pubmed
Franks,
Structural basis for the inhibition of firefly luciferase by a general anesthetic.
1998,
Pubmed
Garrett,
Enhancement of gamma-aminobutyric acidA receptor activity by alpha-chloralose.
1998,
Pubmed
,
Xenbase
Garrett,
Pharmacokinetics of trichloroethanol and metabolites and interconversions among variously referenced pharmacokinetic parameters.
1973,
Pubmed
Grenningloh,
The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors.
,
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 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
Hales,
The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones.
1991,
Pubmed
Harris,
Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition.
1995,
Pubmed
Harrison,
Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.
1993,
Pubmed
Ishizuka,
Alpha-chloralose opens the chloride channel of frog isolated sensory neurons.
1989,
Pubmed
Jones,
Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics.
1992,
Pubmed
Koltchine,
Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology.
1996,
Pubmed
Krasowski,
Alpha subunit isoform influences GABA(A) receptor modulation by propofol.
1997,
Pubmed
Krasowski,
General anaesthetic actions on ligand-gated ion channels.
1999,
Pubmed
Krasowski,
Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane.
1998,
Pubmed
Krasowski,
Trichloroethanol modulation of recombinant GABAA, glycine and GABA rho 1 receptors.
1998,
Pubmed
Kuhse,
The inhibitory glycine receptor: architecture, synaptic localization and molecular pathology of a postsynaptic ion-channel complex.
1995,
Pubmed
Lovinger,
Trichloroethanol potentiates synaptic transmission mediated by gamma-aminobutyric acidA receptors in hippocampal neurons.
1993,
Pubmed
MARSHALL,
Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol.
1954,
Pubmed
Mascia,
Enhancement of homomeric glycine receptor function by long-chain alcohols and anaesthetics.
1996,
Pubmed
,
Xenbase
McGurk,
The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor.
1998,
Pubmed
,
Xenbase
Mihic,
Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics.
1996,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Mihic,
Potentiation of gamma-aminobutyric acid type A receptor-mediated chloride currents by novel halogenated compounds correlates with their abilities to induce general anesthesia.
1994,
Pubmed
,
Xenbase
Mihic,
Anaesthetic concentrations of alcohols potentiate GABAA receptor-mediated currents: lack of subunit specificity.
1994,
Pubmed
,
Xenbase
MONROE,
The hypnotic effects of alpha and beta chloralose in rats.
1963,
Pubmed
MONROE,
Anticonvulsant activity of alpha and beta chloralose in rats.
1963,
Pubmed
Nakahiro,
Modulation of gamma-aminobutyric acid receptor-channel complex by alcohols.
1991,
Pubmed
Nakahiro,
General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons.
1989,
Pubmed
Nattel,
Direct electrophysiological actions of pentobarbital at concentrations achieved during general anesthesia.
1990,
Pubmed
Peoples,
Trichloroethanol potentiation of gamma-aminobutyric acid-activated chloride current in mouse hippocampal neurones.
1994,
Pubmed
Pistis,
The interaction of general anaesthetics with recombinant GABAA and glycine receptors expressed in Xenopus laevis oocytes: a comparative study.
1997,
Pubmed
,
Xenbase
Prince,
Steroid modulation of the strychnine-sensitive glycine receptor.
1992,
Pubmed
Pritchett,
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology.
1989,
Pubmed
Robertson,
Actions of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones.
1989,
Pubmed
Thompson,
Barbiturate interactions at the human GABAA receptor: dependence on receptor subunit combination.
1996,
Pubmed
,
Xenbase
Tomlin,
Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid type A receptors and animals.
1998,
Pubmed
Ueno,
Subunit mutations affect ethanol actions on GABA(A) receptors expressed in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Wakamori,
Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat.
1991,
Pubmed
Waud,
On biological assays involving quantal responses.
1972,
Pubmed
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Wu,
Potentiation by sevoflurane of the gamma-aminobutyric acid-induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus.
1996,
Pubmed
