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

  title={Glutathione Is an Endogenous Ligand of Rat Brain N-Methyl-D-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate (AMPA) Receptors},
  author={Vince Varga and Zsolt Jenei and R{\'e}ka Jan{\'a}ky and Pirjo Saransaari and S. S. Oja},
  journal={Neurochemical Research},
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… 

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

The endogenous S-methylglutathione and glutathione sulfonate and the synthetic S-alkyl derivatives of glutathion act as ligands of the AMPA and NMDA receptors and in the NMDA receptor-ionophore.

Interference of S-Nitrosoglutathione with the Binding of Ligands to Ionotropic Glutamate Receptors in Pig Cerebral Cortical Synaptic Membranes

It is assumed that GSNO may act as an endogenous ligand at the NMDA and non-NMDA classes of glutamate receptors and facilitate NO transfer and target its delivery to specific sites in these receptors.

Modulation of [3H]Dopamine Release by Glutathione in Mouse Striatal Slices

Glutathione alone does not directly evoke dopamine release but may inhibit the depolarization-evoked release by preventing the toxic effects of high glutamate, and by modulating the cysteine–cystine redox state in Ca2+ channels.

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

NMDA receptor stimulation cause an increased selective efflux of glutathione, phosphoethanolamine and taurine in organotypic cultures of rat hippocampus, and the efflux may partly be regulated by calmodulin and DNDS sensitive channels.

S-Nitrosoglutathione and glutathione act as NMDA receptor agonists in cultured hippocampal neurons

Combined pre- and postnatal morphine exposure does not modulate NMDA receptor signaling in the cultured hippocampal neurons and the maximal responses and the EC50 values for the glutamate, NMDA, GSNO, and glutathione-induced [Ca2+]i increases and the glutathion-induced glutamate release were indistinguishable in the neurons of the offspring from control and morphine-addicted female rats.

Involvement of Amino-Acid Side Chains of Membrane Proteins in the Binding of Glutathione to Pig Cerebral Cortical Membranes

The results indicate that cysteinyl side chains and disulfide bonds are essential in the binding of GSH to membrane proteins and that arginyl and lysylSide chains may also be directly involved in this process.

Allosteric modulation of the calcium-sensing receptor by gamma-glutamyl peptides: inhibition of PTH secretion, suppression of intracellular cAMP levels, and a common mechanism of action with L-amino acids.

It is found that γ-glutamyl peptides are potent positive allosteric modulators of the CaR that promote Ca(2+)(o)-dependent Ca( 2+)(i) mobilization, suppress intracellular cAMP levels and inhibit PTH secretion from normal human parathyroid cells.

Dynamic or inert metabolism? Turnover of N‐acetyl aspartate and glutathione from d‐[1‐13C]glucose in the rat brain in vivo

It is concluded that NAA and GSH are completely turned over and that the metabolism is extremely slow (< 0.05% of the glucose metabolic rate).



Different modes of action of 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid in the modulation of N-methyl-D-aspartate-sensitive glutamate receptors.

The results demonstrate that Cl-KYN and HA-966 differ in their ability to modulate the NMDA receptor, perhaps acting at distinct but overlapping recognition sites and suggest that agonist and antagonist recognition sites of the NMda receptor may be independently regulated by glycine and HA -966, which would result in a positive and negative allosteric modulation of theNMDA receptor complex.

3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine.

Glycine regulated 3H-labeled MK-801 binding, and enhanced the ability of N-methyl-D-aspartate to increase Ca2+ influx into primary cultures of mouse striatal neurons measured using the Ca2-sensitive fluorescent dye fura-2.

Effects of thiol-reagents on [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to rat telencephalic membranes.

The results suggest that free sulfhydryl groups allosterically modulate the affinity of the quisqualate subtype of excitatory amino acid receptors and also indicate that different types of glutamate receptors might be differentially affected by chemical modification.

Stimulation of N-methyl-D-aspartate receptor-mediated calcium entry into dissociated neurons by reduced and oxidized glutathione.

The results suggest the potential for modulation of the NMDA receptor complex by GSH and GSSG using fura-2-loaded dissociated brain cells from newborn rat pups and the idea that these effects are mediated, at least in part, by interaction with theNMDA receptor was supported.

Characterization of quisqualate recognition sites in rat brain tissue usingDl-[3H]α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and a filtration assay

The present technique provides a rapid, reliable assay for the evaluation of quisqualate-type excitatory amino acid agonists and/or antagonists that may be used to discover more potent and selective agents.