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Positive allosteric modulators differentially affect full versus partial agonist activation of the glycine receptor.
Kirson D
,
Todorovic J
,
Mihic SJ
.
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Taurine acts as a partial agonist at the glycine receptor (GlyR) in some brain regions such as the hippocampus, striatum, and nucleus accumbens. Ethanol, volatile anesthetics, and inhaled drugs of abuse are all known positive allosteric modulators of GlyRs, but their effects on taurine-activated GlyRs remain poorly understood, especially their effects on the high concentrations of taurine likely to be found after synaptic release. Two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes was used to compare the enhancing effects of ethanol, anesthetics, and inhalants on human homomeric α1-GlyR activated by saturating concentrations of glycine versus taurine. Allosteric modulators had negligible effects on glycine-activated GlyR while potentiating taurine-activated currents. In addition, inhaled anesthetics markedly enhanced desensitization rates of taurine- but not glycine-activated receptors. Our findings suggest that ethanol, volatile anesthetics, and inhalants differentially affect the time courses of synaptic events at GlyR, depending on whether the receptor is activated by a full or partial agonist.
Albrecht,
Taurine interaction with neurotransmitter receptors in the CNS: an update.
2005, Pubmed
Albrecht,
Taurine interaction with neurotransmitter receptors in the CNS: an update.
2005,
Pubmed
Baer,
Localization of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: an immunohistochemical review.
2009,
Pubmed
Beato,
The activation mechanism of alpha1 homomeric glycine receptors.
2004,
Pubmed
Beckstead,
Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.
2000,
Pubmed
,
Xenbase
Beckstead,
Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor function.
2001,
Pubmed
,
Xenbase
Beckstead,
Anesthetic and ethanol effects on spontaneously opening glycine receptor channels.
2002,
Pubmed
,
Xenbase
Bowen,
The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies.
2006,
Pubmed
Chau,
New insights into the molecular mechanisms of general anaesthetics.
2010,
Pubmed
Cheng,
Pre- and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons.
2002,
Pubmed
Dahchour,
Taurine increases in the nucleus accumbens microdialysate after acute ethanol administration to naive and chronically alcoholised rats.
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
Ericson,
Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine.
2006,
Pubmed
Ericson,
Rising taurine and ethanol concentrations in nucleus accumbens interact to produce dopamine release after ethanol administration.
2011,
Pubmed
Evans,
CNS depressant effects of volatile organic solvents.
1991,
Pubmed
Franks,
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal.
2008,
Pubmed
Gardner,
Conductances of single ion channels opened by nicotinic agonists are indistinguishable.
,
Pubmed
Lape,
On the nature of partial agonism in the nicotinic receptor superfamily.
2008,
Pubmed
Lewis,
Kinetic determinants of agonist action at the recombinant human glycine receptor.
2003,
Pubmed
Lu,
Glycine-activated chloride currents of neurons freshly isolated from the prefrontal cortex of young rats.
2011,
Pubmed
Lubman,
Inhalant abuse among adolescents: neurobiological considerations.
2008,
Pubmed
Lynch,
Molecular structure and function of the glycine receptor chloride channel.
2004,
Pubmed
Mascia,
A single amino acid determines differences in ethanol actions on strychnine-sensitive glycine receptors.
1996,
Pubmed
,
Xenbase
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Mihic,
Acute effects of ethanol on GABAA and glycine receptor function.
1999,
Pubmed
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
Molander,
The glycine reuptake inhibitor Org 25935 decreases ethanol intake and preference in male wistar rats.
2007,
Pubmed
Molander,
Involvement of accumbal glycine receptors in the regulation of voluntary ethanol intake in the rat.
2005,
Pubmed
Mori,
Beta-alanine and taurine as endogenous agonists at glycine receptors in rat hippocampus in vitro.
2002,
Pubmed
Roberts,
Occupancy of a single anesthetic binding pocket is sufficient to enhance glycine receptor function.
2006,
Pubmed
,
Xenbase
Rodríguez-Navarro,
High potassium induces taurine release by osmosensitive and osmoresistant mechanisms in the rat hippocampus in vivo.
2009,
Pubmed
Shibanoki,
Effect of systemic administration of N-methyl-D-aspartic acid on extracellular taurine level measured by microdialysis in the hippocampal CA1 field and striatum of rats.
1993,
Pubmed
Wang,
Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats.
2005,
Pubmed
Welsh,
Ethanol enhances taurine-activated glycine receptor function.
2010,
Pubmed
,
Xenbase
Welsh,
Single-channel analysis of ethanol enhancement of glycine receptor function.
2009,
Pubmed
,
Xenbase
Yamakura,
Amino acid volume and hydropathy of a transmembrane site determine glycine and anesthetic sensitivity of glycine receptors.
1999,
Pubmed
,
Xenbase
Yamashita,
Modulation of miniature inhibitory postsynaptic currents by isoflurane in rat dissociated neurons with glycinergic synaptic boutons.
2001,
Pubmed
Ye,
Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267.
1998,
Pubmed
,
Xenbase
Yevenes,
Allosteric modulation of glycine receptors.
2011,
Pubmed