Neurochemical Research

, Volume 23, Issue 8, pp 1085–1091 | Cite as

Interference of S-Alkyl Derivatives of Glutathione with Brain Ionotropic Glutamate Receptors

  • Zsolt Jenei
  • Réka Janáky
  • Vince Varga
  • Pirjo Saransaari
  • Simo S. Oja
Article

Abstract

The effects of glutathione, glutathione sulfonate and S-alkyl derivatives of glutathione on the binding of glutamate and selective ligands of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors were studied with mouse synaptic membranes. The effects of glutathione and its analogues on 45Ca2+ influx were also estimated in cultured rat cerebellar granule cells. Reduced and oxidized glutathione, glutathione sulfonate, S-methyl-, -ethyl-, -propyl-, -butyl- and -pentylglutathione inhibited the Na+-independent binding of L-[3H]glutamate. They strongly inhibited also the binding of (S)-2-amino-3-hydroxy-5-[3H]methyl-4-isoxazolepropionate [3H]AMPA (IC50 values: 0.8–15.9 μM). S-Alkylation of glutathione rendered the derivatives unable to inhibit [3H]kainate binding. The NMDA-sensitive binding of L-[3H]glutamate and the binding of 3-[(R)-2-carboxypiperazin-4-yl][1,2-3H]propyl-1-phosphonate ([3H]CPP, a competitive antagonist at NMDA sites) were inhibited by the peptides at micromolar concentrations. The strychnine-insensitive binding of the NMDA coagonist [3H]glycine was attenuated only by oxidized glutathione and glutathione sulfonate. All peptides slightly enhanced the use-dependent binding of [3H]dizocilpine (MK-801) to the NMDA-gated ionophores. This effect was additive with the effect of glycine but not with that of saturating concentrations of glutamate or glutamate plus glycine. The glutamate- and NMDA-evoked influx of 45Ca2+ into cerebellar granule cells was inhibited by the S-alkyl derivatives of glutathione. We conclude that besides glutathione the endogenous S-methylglutathione and glutathione sulfonate and the synthetic S-alkyl derivatives of glutathione act as ligands of the AMPA and NMDA receptors. In the NMDA receptor-ionophore these glutathione analogues bind preferably to the glutamate recognition site via their γ-glutamyl moieties.

Glutamate receptors glutathione derivatives ligand binding Ca2+ influx 

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Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Zsolt Jenei
    • 1
    • 2
  • Réka Janáky
    • 1
  • Vince Varga
    • 1
    • 2
  • Pirjo Saransaari
    • 1
  • Simo 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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