Neurochemical Research

, Volume 22, Issue 9, pp 1165–1171 | Cite as

Glutathione Is an Endogenous Ligand of Rat Brain N-Methyl-D-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate (AMPA) Receptors

  • V. Varga
  • Zs. Jenei
  • R. Janáky
  • P. Saransaari
  • S. S. Oja


A study was made of the effects of reduced (GSH) and oxidized (GSSG) glutathione on the Na+-independent and N-methyl-D-aspartate (NMDA) displaceable bindings of glutamate, on the binding of kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ligands of the brain NMDA receptor-ionophore complex: glycine, dizocilpine (MK-801) and (±)-3-(2-car-boxypiperazin-4-yl)propyl-1-phosphonate (CPP). GSH and GSSG strongly inhibited the binding of glutamate, CPP and AMPA, kainate and glycine binding being less affected. Both peptides enhanced the binding of dizocilpine in a time- and concentration-dependent manner. This activatory effect was not additive to that of saturating concentrations of glutamate or glutamate plus glycine. The activation of dizocilpine binding by GSH and GSSG was prevented by the competitive NMDA and glycine antagonists DL-2-amino-5-phosphonovalerate and 7-chlorokynurenate. GSH and GSSG may be endogenous ligands of AMPA and NMDA receptors, binding preferably to the glutamate recognition site via their γ-glutamyl moieties. In addition to this, at millimolar concentrations they may regulate the redox state of the NMDA receptor-ionophore complex.

Glutamate receptors endogenous regulator reduced and oxidized glutathione 


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Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • V. Varga
    • 1
    • 2
  • Zs. Jenei
    • 1
    • 2
  • R. Janáky
    • 1
  • P. Saransaari
    • 1
  • S. S. Oja
    • 1
    • 3
  1. 1.Tampere Brain Research CenterUniversity of Tampere Medical SchoolTampereFinland
  2. 2.Department of Animal PhysiologyKossuth Lajos University of SciencesDebrecenHungary
  3. 3.Department of Clinical PhysiologyTampere University HospitalTampereFinland

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