title: Differential effects of zinc on glutamatergic and GABAergic neurotransmitter systems in the hippocampus.
abstract: Approximately 10% of total zinc in the brain exists in synaptic vesicles of glutamatergic neurons; however, the function of vesicular zinc is poorly understood. The presynaptic action of zinc against excitatory and inhibitory neurotransmission was studied in rat hippocampus using in vivo microdialysis. When the hippocampal CA3 region was perfused with 10-300 microM ZnCl(2), the level of glutamate in the perfusate was decreased, whereas the level of gamma-aminobutyric acid (GABA) was increased. Chelation of endogenous zinc with CaEDTA increased the glutamate level in the perfusate but decreased the GABA level, suggesting that zinc released into the synaptic cleft acts differentially on glutamatergic and GABAergic neurons in the CA3 region. The increase of GABA level by zinc was antagonized by 2,3-dioxo-6-nitro-1,2.3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide (NBQX), an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors, but not affected by MK801, an antagonist of N-methyl-D-aspartate (NMDA) receptors, and verapamil, a blocker of voltage-dependent calcium channels. The present study suggests that zinc enhances GABA release via potentiation of AMPA/kainate receptors in the CA3 region, followed by a decrease in presynaptic glutamate release in the same region. Zinc seems to be an inhibitory neuromodulator of glutamate release.
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Minami
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017967:Zinc Compounds; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; C016837:zinc chloride; D015032:Zinc