Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
paper
Cited
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- Authors
- Mihic, S J; Ye, Q; Wick, M J; Koltchine, V V; Krasowski, M D; Finn, S E; Mascia, M P; Valenzuela, C F; Hanson, K K; Greenblatt, E P; Harris, R A; Harrison, N L
- Year
- 1997
- Journal
- Nature
- PMID
- 9311780
- DOI
- 10.1038/38738
Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.
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| The L293 residue in transmembrane domain 2 of the 5-HT3A receptor is a molecular determinant of allosteric modulation by 5-hydroxyindole. | Hu XQ et al. | β | 2008 | β |
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| Volatile anesthetics and endogenous cannabinoid anandamide have additive and independent inhibitory effects on alpha(7)-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes. | Jackson SN et al. | β | 2008 | β |
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| Beta-subunits are important modulators of the acute response to alcohol in human BK channels. | Feinberg-Zadek PL et al. | β | 2007 | β |
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| Channel opening by anesthetics and GABA induces similar changes in the GABAA receptor M2 segment. | Rosen A et al. | β | 2007 | β |
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| Comparison of lorazepam [7-chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one] occupancy of rat brain gamma-aminobutyric acid(A) receptors measured using in vivo [3H]flumazenil (8-fluoro 5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester) binding and [11C]flumazenil micro-positron emission tomography. | Atack JR et al. | β | 2007 | β |
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| Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors. | Hanchar HJ et al. | β | 2006 | β |
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| Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11. | Hood HM et al. | β | 2006 | β |
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| Occupancy of a single anesthetic binding pocket is sufficient to enhance glycine receptor function. | Roberts MT et al. | β | 2006 | β |
| Partitioning of anesthetics into a lipid bilayer and their interaction with membrane-bound peptide bundles. | Vemparala S et al. | β | 2006 | β |
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| Residues in the first transmembrane domain of the Caenorhabditis elegans GABA(A) receptor confer sensitivity to the neurosteroid pregnenolone sulfate. | Wardell B et al. | β | 2006 | β |
| Resolution improvement in positron emission tomography using anatomical Magnetic Resonance Imaging. | Chu Y et al. | β | 2006 | β |
| Sites in TM2 and 3 are critical for alcohol-induced conformational changes in GABA receptors. | Jung S et al. | β | 2006 | β |
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| Structural constraints for alcohol-stimulated Ca2+ release in neural crest, and dual agonist/antagonist properties of n-octanol. | Garic-Stankovic A et al. | β | 2006 | β |
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| Differential GABAB Receptor Modulation of Ethanol Effects on GABA(A) synaptic activity in hippocampal CA1 neurons. | Wu PH et al. | β | 2005 | β |
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| Ethanol-response genes and their regulation analyzed by a microarray and comparative genomic approach in the nematode Caenorhabditis elegans. | Kwon JY et al. | β | 2004 | β |
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| A single glycine residue at the entrance to the first membrane-spanning domain of the gamma-aminobutyric acid type A receptor beta(2) subunit affects allosteric sensitivity to GABA and anesthetics. | Carlson BX et al. | β | 2000 | β |
| A transmembrane site determines sensitivity of neuronal nicotinic acetylcholine receptors to general anesthetics. | Yamakura T et al. | β | 2000 | β |
| Benzodiazepines act on GABAA receptors via two distinct and separable mechanisms. | Walters RJ et al. | β | 2000 | β |
| Benzodiazepines induce a conformational change in the region of the gamma-aminobutyric acid type A receptor alpha(1)-subunit M3 membrane-spanning segment. | Williams DB et al. | β | 2000 | β |
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| Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. | Kane NS et al. | β | 2000 | β |
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| Effect of halothane on the oligomerization of the sarcoplasmic reticulum Ca(2+)-ATPase. | Brennan LK et al. | β | 2000 | β |
| Enhanced locomotor stimulation by NMDA receptor antagonists in alcohol-sensitive ANT rats. | Vekovischeva OY et al. | β | 2000 | β |
| Ethanol inhibits insulin receptor tyrosine kinase. | Seiler AE et al. | β | 2000 | β |
| General anesthetic action at an internal protein site involving the S4-S5 cytoplasmic loop of a neuronal K(+) channel. | Harris T et al. | β | 2000 | β |
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| Glycine receptor beta subunits play a critical role in potentiation of glycine responses by ICS-205,930. | Supplisson S et al. | β | 2000 | β |
| Identification of an amino acid defining the distinct properties of murine beta1 and beta3 subunit-containing GABA(A) receptors. | Cestari IN et al. | β | 2000 | β |
| Identification of sites of incorporation in the nicotinic acetylcholine receptor of a photoactivatible general anesthetic. | Pratt MB et al. | β | 2000 | β |
| Inhibition of the human intermediate conductance Ca(2+)-activated K(+) channel, hIK1, by volatile anesthetics. | Namba T et al. | β | 2000 | β |
| Is anesthesia caused by potentiation of synaptic or intrinsic inhibition? Recent insights into the mechanisms of volatile anesthetics. | Perouansky M et al. | β | 2000 | β |
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| Mechanisms of anaesthesia: time to say farewell to the Meyer-Overton rule. | Bovill JG | β | 2000 | β |
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| Naturally occurring variability in anesthetic potency among inbred mouse strains. | Sonner JM et al. | β | 2000 | β |
| Nicotinic receptor pore mutations create a sensitive inhibitory site for ethanol. | Forman SA et al. | β | 2000 | β |
| NMR study of volatile anesthetic binding to nicotinic acetylcholine receptors. | Xu Y et al. | β | 2000 | β |
| Nociceptin/orphanin FQ and drugs of abuse. | Ciccocioppo R et al. | β | 2000 | β |
| P2-purinergic receptor antagonists reduce the minimum alveolar concentration of inhaled volatile anesthetics. | Masaki E et al. | β | 2000 | β |
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| The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. | Krasowski MD et al. | β | 2000 | β |
| The anesthetic potency of propanol and butanol versus propanethiol and butanethiol in alpha1 wild type and alpha1(S267Q) glycine receptors. | Mascia MP et al. | β | 2000 | β |
| The exhaustive additivity displayed by nitrous oxide has implications for cognitive-energetical theory. | Fowler B et al. | β | 2000 | β |
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| A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. | van Swinderen B et al. | β | 1999 | β |
| A single amino acid confers barbiturate sensitivity upon the GABA rho 1 receptor. | Belelli D et al. | β | 1999 | β |
| A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors. | Dalziel JE et al. | β | 1999 | β |
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| Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery. | Zaugg M et al. | β | 1999 | β |
| Bound volatile general anesthetics alter both local protein dynamics and global protein stability. | Johansson JS et al. | β | 1999 | β |
| Cell membrane dynamics and the induction of apoptosis by lipid compounds. | Fujimoto K et al. | β | 1999 | β |
| Cerebellar granule-cell-specific GABAA receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice. | Korpi ER et al. | β | 1999 | β |
| Characterization of the electrophysiological and pharmacological effects of 4-iodo-2,6-diisopropylphenol, a propofol analogue devoid of sedative-anaesthetic properties. | Sanna E et al. | β | 1999 | β |
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| Distinctly different interactions of anesthetic and nonimmobilizer with transmembrane channel peptides. | Tang P et al. | β | 1999 | β |
| Drugs of abuse and brain gene expression. | Torres G et al. | β | 1999 | β |
| Dual actions of volatile anesthetics on GABA(A) IPSCs: dissociation of blocking and prolonging effects. | Banks MI et al. | β | 1999 | β |
| Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. | Cardoso RA et al. | β | 1999 | β |
| Effects of halothane on synaptic neurotransmission to medullary expiratory neurons in the ventral respiratory group of dogs. | Stuth EA et al. | β | 1999 | β |
| Effects of temperature and volatile anesthetics on GABA(A) receptors. | Jenkins A et al. | β | 1999 | β |
| Ethanol actions on multiple ion channels: which are important? | Harris RA | β | 1999 | β |
| Ethanol and protein kinase C. | Stubbs CD et al. | β | 1999 | β |
| Ethanol opens G-protein-activated inwardly rectifying K+ channels. | Kobayashi T et al. | β | 1999 | β |
| Gamma-aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in gamma-aminobutyric acid type A receptors. | Williams DB et al. | β | 1999 | β |
| GAS-1: a mitochondrial protein controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans. | Kayser EB et al. | β | 1999 | β |
| General anaesthetic action at transmitter-gated inhibitory amino acid receptors. | Belelli D et al. | β | 1999 | β |
| General anaesthetic actions on ligand-gated ion channels. | Krasowski MD et al. | β | 1999 | β |
| Halothane presynaptically depresses synaptic transmission in wild-type Drosophila larvae but not in halothane-resistant (har) mutants. | Nishikawa K et al. | β | 1999 | β |
| Human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes predict efficacy of halogenated compounds that disobey the Meyer-Overton rule. | Cardoso RA et al. | β | 1999 | β |
| Identification of transduction elements for benzodiazepine modulation of the GABA(A) receptor: three residues are required for allosteric coupling. | Boileau AJ et al. | β | 1999 | β |
| Inhalational anesthetics activate two-pore-domain background K+ channels. | Patel AJ et al. | β | 1999 | β |
| Isoflurane increases the apparent agonist affinity of the nicotinic acetylcholine receptor. | Raines DE et al. | β | 1999 | β |
| Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer. | Detsch O et al. | β | 1999 | β |
| Lipid binding to sterol carrier protein-2 is inhibited by ethanol. | Avdulov NA et al. | β | 1999 | β |
| Mechanisms of action of drugs of abuse on the developing fetal brain. | Malanga CJ et al. | β | 1999 | β |
| Mode of action of ICS 205,930, a novel type of potentiator of responses to glycine in rat spinal neurones. | Chesnoy-Marchais D | β | 1999 | β |
| Molecular and functional diversity of the expanding GABA-A receptor gene family. | Whiting PJ et al. | β | 1999 | β |
| Molecular dynamics simulation of a synthetic four-alpha-helix bundle that binds the anesthetic halothane. | Davies LA et al. | β | 1999 | β |
| Molecular simulation of the effects of alcohols on peptide structure. | Dwyer DS | β | 1999 | β |
| Mutant human alpha(1)beta(1)(T262Q) GABA(A) receptors are directly activated but not modulated by pentobarbital. | Dalziel JE et al. | β | 1999 | β |
| Mutation of putative phosphorylation sites in the 5-hydroxytryptamine3 receptor does not eliminate its modulation by ethanol. | Machu TK et al. | β | 1999 | β |
| Neurosteroids mediate pharmacological effects of ethanol: a new mechanism of ethanol action? | Morrow AL et al. | β | 1999 | β |
| Nonimmobilizers and transitional compounds may produce convulsions by two mechanisms. | Eger EI et al. | β | 1999 | β |
| Partitioning of four modern volatile general anesthetics into solvents that model buried amino acid side-chains. | Johansson JS et al. | β | 1999 | β |
| Potassium channels: basic aspects, functional roles, and medical significance. | Yost CS | β | 1999 | β |
| Preparation of barbiturate optical isomers and their effects on GABA(A) receptors. | Tomlin SL et al. | β | 1999 | β |
| Recent advances in GABA research. | Kardos J | β | 1999 | β |
| Recent advances in the pharmacology of quaternary salts of bicuculline. | Seutin V et al. | β | 1999 | β |
| Selective blocking effects of tropisetron and atropine on recombinant glycine receptors. | Maksay G et al. | β | 1999 | β |
| Sevoflurane-induced reduction of hypoxic drive is sex-independent. | Sarton E et al. | β | 1999 | β |
| Stable expression of human glycine alpha1 and alpha2 homomeric receptors in mouse L(tk-) cells. | Wick MJ et al. | β | 1999 | β |
| Structural consequences of anesthetic and nonimmobilizer interaction with gramicidin A channels. | Tang P et al. | β | 1999 | β |
| Structure-activity relationship of alkanols as mosquito larvicides with novel findings regarding their mode of action. | Hammond DG et al. | β | 1999 | β |
| Subunit mutations affect ethanol actions on GABA(A) receptors expressed in Xenopus oocytes. | Ueno S et al. | β | 1999 | β |
| Synthesis and properties of 3-(2-hydroxyethyl)-3-n-pentyldiazirine, a photoactivable general anesthetic. | Husain SS et al. | β | 1999 | β |
| The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor. | Bamber BA et al. | β | 1999 | β |
| The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics. | Fukami S et al. | β | 1999 | β |
| The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. | Wakasugi M et al. | β | 1999 | β |
| The GABA-A receptor gene family: new targets for therapeutic intervention. | Whiting PJ | β | 1999 | β |
| The interaction of general anaesthetics and neurosteroids with GABA(A) and glycine receptors. | Belelli D et al. | β | 1999 | β |
| Volatile and local anesthetics interfere with thromboxane A2 receptors recombinantly expressed in Xenopus oocytes. | HΓΆnemann CW et al. | β | 1999 | β |
| Volatile anesthetic inhibition of neuronal Ca channel currents expressed in Xenopus oocytes. | Kamatchi GL et al. | β | 1999 | β |
| Volatile anesthetics block actin-based motility in dendritic spines. | Kaech S et al. | β | 1999 | β |
| Volatile anesthetics modulate the binding of guanine nucleotides to the alpha subunits of heterotrimeric GTP binding proteins. | Pentyala SN et al. | β | 1999 | β |
| Alcohol and benzodiazepines: recent mechanistic studies. | Harris RA et al. | β | 1998 | β |
| Alcohol effects on the 5-HT3 ligand-gated ion channel. | Lovinger DM et al. | β | 1998 | β |
| AMPA/kainate receptor antagonists as novel analgesic agents. | Brennan TJ | β | 1998 | β |
| Approaches to proving there are general anesthetic sites on ligand gated ion channels. | Miller KW et al. | β | 1998 | β |
| Contributions of dipole moments, quadrupole moments, and molecular polarizabilities to the anesthetic potency of fluorobenzenes. | Trudell JR | β | 1998 | β |
| Differential sensitivities of TTX-resistant and TTX-sensitive sodium channels to anesthetic concentrations of ethanol in rat sensory neurons. | Wu JV et al. | β | 1998 | β |
| Direct antagonism of ethanol's effects on GABA(A) receptors by increased atmospheric pressure. | Davies DL et al. | β | 1998 | β |
| Drug-activation of brain reward pathways. | Wise RA | β | 1998 | β |
| Effects of anesthetics on the structure of a phospholipid bilayer: molecular dynamics investigation of halothane in the hydrated liquid crystal phase of dipalmitoylphosphatidylcholine. | Tu K et al. | β | 1998 | β |
| Effects of ethanol on recombinant glycine receptors expressed in mammalian cell lines. | Valenzuela CF et al. | β | 1998 | β |
| Effects of isoflurane on [Ca2+]i, SR Ca2+ content, and twitch force in intact trabeculae. | Jiang Y et al. | β | 1998 | β |
| Effects of moderate alcohol consumption on the central nervous system. | Eckardt MJ et al. | β | 1998 | β |
| Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267. | Ye Q et al. | β | 1998 | β |
| Enhancement of glycine receptor function by ethanol: role of phosphorylation. | Mascia MP et al. | β | 1998 | β |
| Ethanol and neurotransmitter interactions--from molecular to integrative effects. | Faingold CL et al. | β | 1998 | β |
| Ethanol concentrations approaching minimum alveolar anesthetic concentration are required to suppress learning in a fear-potentiated startle paradigm in rats. | Sonner JM et al. | β | 1998 | β |
| Etomidate revisited. | Ostwald P et al. | β | 1998 | β |
| How does xenon produce anaesthesia? | Franks NP et al. | β | 1998 | β |
| Ion channel modulation as the basis for general anesthesia. | Narahashi T et al. | β | 1998 | β |
| Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor? | Wick MJ et al. | β | 1998 | β |
| Neural basis of inhalant abuse. | Balster RL | β | 1998 | β |
| Occupation of the cytochrome P450 substrate pocket by diverse compounds at general anesthesia concentrations. | LaBella FS et al. | β | 1998 | β |
| Optical isomers open a new window on anesthetic mechanism. | Harrison NL | β | 1998 | β |
| Propofol analogues. Synthesis, relationships between structure and affinity at GABAA receptor in rat brain, and differential electrophysiological profile at recombinant human GABAA receptors. | Trapani G et al. | β | 1998 | β |
| Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. | Krasowski MD et al. | β | 1998 | β |
| Sites of volatile anesthetic action on kainate (Glutamate receptor 6) receptors. | Minami K et al. | β | 1998 | β |
| Structural basis for the inhibition of firefly luciferase by a general anesthetic. | Franks NP et al. | β | 1998 | β |
| The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor. | McGurk KA et al. | β | 1998 | β |
| The lipid/protein interface as a target site for general anesthetics: a multiple-site kinetic analysis of synaptosomal Ca2+-ATPase. | Pflugmacher D et al. | β | 1998 | β |
| The molecular mechanism of action of general anesthetics: structural aspects of interactions with GABA(A) receptors. | Olsen RW | β | 1998 | β |
| Unc-1: a stomatin homologue controls sensitivity to volatile anesthetics in Caenorhabditis elegans. | Rajaram S et al. | β | 1998 | β |
| Volatile anesthetics directly activate baseline S K+ channels in aplysia neurons. | Winegar BD et al. | β | 1998 | β |
| Which molecular targets are most relevant to general anaesthesia? | Franks NP et al. | β | 1998 | β |
| Anaesthetics in a bind? | Peters JA et al. | β | 1997 | β |
| The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid. | Belelli D et al. | β | 1997 | β |