General anaesthetic action at transmitter-gated inhibitory amino acid receptors.

Research within the past decade has provided compelling evidence that anaesthetics can act directly as allosteric modulators of transmitter-gated ion channels. Recent comparative studies of the effects of general anaesthetics across a structurally homologous family of inhibitory amino acid receptors that includes mammalian GABAA, glycine and Drosophila RDL GABA receptors have provided new insights into the structural basis of anaesthetic action at transmitter-gated channels. In this article, the differential effects of general anaesthetics across inhibitory amino acid receptors and the potential relevance of such actions to general anaesthesia will be discussed.

[1]  M. Pistis,et al.  The effect of a transmembrane amino acid on etomidate sensitivity of an invertebrate GABA receptor , 1998, British journal of pharmacology.

[2]  J. Benson,et al.  Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes , 1999, Nature.

[3]  J. A. Peters,et al.  Subunit‐dependent interaction of the general anaesthetic etomidate with the γ‐aminobutyric acid type A receptor , 1997, British journal of pharmacology.

[4]  J. Sikela,et al.  Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit. , 1996, Molecular pharmacology.

[5]  R. Eckenhoff,et al.  Steric hindrance is not required for n-alkanol cutoff in soluble proteins. , 1999, Molecular pharmacology.

[6]  E A Barnard,et al.  International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. , 1998, Pharmacological reviews.

[7]  J. Reynolds,et al.  Modulatory and direct effects of propofol on recombinant GABAA receptors expressed in Xenopus oocytes: Influence of α- and γ 2-subunits , 1998, Brain Research.

[8]  M. Santi,et al.  Neurosteroids act on recombinant human GABAA receptors , 1990, Neuron.

[9]  E. Sigel,et al.  The benzodiazepine binding site of GABAA receptors. , 1997, Trends in pharmacological sciences.

[10]  M. Bianchi,et al.  Spontaneous and gamma-aminobutyric acid (GABA)-activated GABA(A) receptor channels formed by epsilon subunit-containing isoforms. , 1999, Molecular pharmacology.

[11]  S. Moss,et al.  Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties. , 1996, Molecular pharmacology.

[12]  A. Jenkins,et al.  Preparation of barbiturate optical isomers and their effects on GABA(A) receptors. , 1999, Anesthesiology.

[13]  C. Zorumski,et al.  Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia. , 1996, Molecular pharmacology.

[14]  A. Pohorille,et al.  Hypothesis: Inhaled Anesthetics Produce Immobility and Amnesia by Different Mechanisms at Different Sites , 1997, Anesthesia and analgesia.

[15]  C. Rick,et al.  α Subunit isoform influences GABAA receptor modulation by propofol , 1997, Neuropharmacology.

[16]  A. Jenkins,et al.  Stereoselective Effects of Etomidate Optical Isomers on Gamma‐aminobutyric Acid Type A Receptors and Animals , 1998, Anesthesiology.

[17]  T. Yamakura,et al.  Amino Acid Volume and Hydropathy of a Transmembrane Site Determine Glycine and Anesthetic Sensitivity of Glycine Receptors* , 1999, The Journal of Biological Chemistry.

[18]  R. Harris,et al.  Subunit mutations affect ethanol actions on GABAA receptors expressed in Xenopus oocytes , 1999, British journal of pharmacology.

[19]  J. A. Peters,et al.  A single amino acid confers barbiturate sensitivity upon the GABA ρ1 receptor , 1999 .

[20]  J. Olney,et al.  Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin , 1998, Nature Medicine.

[21]  N. Harrison,et al.  General anaesthetic actions on ligand-gated ion channels , 1999, Cellular and Molecular Life Sciences CMLS.

[22]  M. Akabas,et al.  Identification of channel-lining residues in the M2 membrane-spanning segment of the GABA(A) receptor alpha1 subunit , 1996, The Journal of general physiology.

[23]  M Pistis,et al.  The interaction of general anaesthetics with recombinant GABAA and glycine receptors expressed in Xenopus laevis oocytes: a comparative study , 1997, British journal of pharmacology.

[24]  B. Antkowiak,et al.  Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor. , 1999, Anesthesiology.

[25]  R. Dickinson,et al.  How does xenon produce anaesthesia? , 1998, Nature.

[26]  R. Harris,et al.  Enhancement of Glycine Receptor Function by Ethanol Is Inversely Correlated with Molecular Volume at Position α267* , 1998, The Journal of Biological Chemistry.

[27]  J. Amin,et al.  Differential modulation of the gamma-aminobutyric acid type C receptor by neuroactive steroids. , 1999, Molecular pharmacology.

[28]  P. Whiting,et al.  Residues in transmembrane domains I and II determine gamma-aminobutyric acid type AA receptor subtype-selective antagonism by furosemide. , 1999, Molecular pharmacology.

[29]  P. Whiting,et al.  Neuronally Restricted RNA Splicing Regulates the Expression of a Novel GABAA Receptor Subunit Conferring Atypical Functional Properties , 1997, The Journal of Neuroscience.

[30]  P. Whiting,et al.  The influence of the γ2L subunit on the modulation of responses to GABAA receptor activation , 1993 .

[31]  J. A. Peters,et al.  Interaction of positive allosteric modulators with human and Drosophila recombinant GABA receptors expressed in Xenopus laevis oocytes , 1996, British journal of pharmacology.

[32]  N. Harrison,et al.  Potentiation of gamma-aminobutyric acidA receptor Cl- current correlates with in vivo anesthetic potency. , 1994, The Journal of pharmacology and experimental therapeutics.

[33]  W. R. Lieb,et al.  Molecular and cellular mechanisms of general anaesthesia , 1994, Nature.

[34]  R. Macdonald,et al.  Assembly of GABAA receptor subunits: role of the delta subunit , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  P. Schofield,et al.  A single amino acid determines differences in ethanol actions on strychnine-sensitive glycine receptors. , 1996, Molecular pharmacology.

[36]  J. Amin A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor. , 1999, Molecular pharmacology.

[37]  L. Firestone,et al.  Anesthesia Sensitivity in Mice that Lack the β3 Subunit of the γ-Aminobutyric Acid Type A Receptor , 1998 .

[38]  N L Harrison,et al.  Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. , 1998, Molecular pharmacology.

[39]  J. Sikela,et al.  Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors. , 1993, Molecular pharmacology.

[40]  R. Harris,et al.  Actions of anesthetics on ligand‐gated ion channels: role of receptor subunit composition , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  R. Miledi,et al.  Subunit‐selective modulation of GABAA receptors by the non‐steroidal anti‐inflammatory agent, mefenamic acid , 1999, The European journal of neuroscience.

[42]  E. Kirkness,et al.  Insensitivity to anaesthetic agents conferred by a class of GABAA receptor subunit , 1997, Nature.

[43]  R. Harris,et al.  Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics , 1996, British journal of pharmacology.

[44]  S. Vicini,et al.  δ Subunit Inhibits Neurosteroid Modulation of GABAAReceptors , 1996, The Journal of Neuroscience.

[45]  Alastair M. Hosie,et al.  Molecular biology of insect neuronal GABA receptors , 1997, Trends in Neurosciences.

[46]  W. R. Lieb,et al.  What is the molecular nature of general anaesthetic target sites , 1987 .

[47]  P. Voorn,et al.  Plasticity in Fast Synaptic Inhibition of Adult Oxytocin Neurons Caused by Switch in GABAA Receptor Subunit Expression , 1997, Neuron.

[48]  I. Módy,et al.  The Role of the GABAA Receptor/Chloride Channel Complex in Anesthesia , 1993, Anesthesiology.

[49]  R. Harris,et al.  Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics. , 1996, The Journal of pharmacology and experimental therapeutics.

[50]  S. Gelman,et al.  Components of anaesthesia. , 1988, British journal of anaesthesia.

[51]  P. Whiting,et al.  Barbiturate interactions at the human GABAA receptor: dependence on receptor subunit combination , 1996, British journal of pharmacology.

[52]  A C Hall,et al.  Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes , 1996, British journal of pharmacology.

[53]  M. Pistis,et al.  Complementary regulation of anaesthetic activation of human (α6β3γ2L) and Drosophila (RDL) GABA receptors by a single amino acid residue , 1999 .

[54]  S. Moss,et al.  Pharmacological and Physiological Characterization of Murine Homomeric β3 GABAA Receptors , 1997, The European journal of neuroscience.

[55]  L. Firestone,et al.  Cerebellar gamma-aminobutyric acid type A receptors: pharmacological subtypes revealed by mutant mouse lines. , 1997, Molecular pharmacology.

[56]  E. Eger,et al.  Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. , 1994, Anesthesia and analgesia.

[57]  R. Harris,et al.  Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors , 1997, Nature.

[58]  R. Harris,et al.  Novel properties of homomeric beta 1 gamma-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital. , 1995, Molecular pharmacology.

[59]  R. Macdonald,et al.  Properties of putative cerebellar gamma-aminobutyric acid A receptor isoforms. , 1996, Molecular pharmacology.

[60]  P. Schofield,et al.  The glycine receptor. , 1997, Pharmacology & therapeutics.

[61]  P. Whiting,et al.  beta-Carboline gamma-aminobutyric acidA receptor inverse agonists modulate gamma-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site. , 1995, Molecular pharmacology.

[62]  G. Lees,et al.  modulation of Recombination Human γ-aminobutyric Acid-a Receptors by Isoflurane : influence of the Delta Subunit , 1998 .