title: Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse.
abstract: Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and α2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation.
authors: Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
authors: Dean
authors: D
authors: Kirson
authors: Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
authors: Garrett L
authors: GL
authors: Cornelison
authors: Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
authors: Ashley E
authors: AE
authors: Philpo
authors: Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA.
authors: Jelena
authors: J
authors: Todorovic
authors: Department of Neuroscience, Division of Pharmacology and Toxicology, Waggoner Center for Alcohol & Addiction Research, Institutes for Neuroscience and Cell & Molecular Biology, University of Texas at Austin, MC A4800, 2500 Speedway, Austin, TX 78712, USA. Electronic address: mihic@austin.utexas.edu.
authors: S John
authors: SJ
authors: Mihic
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008845:Microinjections; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology*; D014131:Trace Elements / Q000494:pharmacology*; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D021122:Protein Subunits; D018009:Receptors, Glycine; D014131:Trace Elements; D013654:Taurine; D000431:Ethanol; D007530:Isoflurane; D015032:Zinc; D005998:Glycine
keywords: Allosteric modulation; EC(5); Ethanol; GlyR; Glycine receptor; Isoflurane; MBS; Modified Barth's Saline; SNK; Student–Newman–Keuls; Toluene; VTA; Zinc; effective concentration producing 5% of maximal effect; glycine receptor; nAcc; nucleus accumbens; ventral tegmental area
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