Neurochemical Research

, Volume 32, Issue 8, pp 1357–1364

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

  • Réka Janáky
  • Róbert Dohovics
  • Pirjo Saransaari
  • Simo S. Oja
Original Paper

DOI: 10.1007/s11064-007-9315-z

Cite this article as:
Janáky, R., Dohovics, R., Saransaari, P. et al. Neurochem Res (2007) 32: 1357. doi:10.1007/s11064-007-9315-z

Abstract

Glutathione (γ-glutamylcysteinylglycine, GSH and oxidized glutathione, GSSG), may function as a neuromodulator at the glutamate receptors and as a neurotransmitter at its own receptors. We studied now the effects of GSH, GSSG, glutathione derivatives and thiol redox agents on the spontaneous, K+- and glutamate-agonist-evoked releases of [3H]dopamine from mouse striatal slices. The release evoked by 25 mM K+ was inhibited by GSH, S-ethyl-, -propyl-, -butyl- and pentylglutathione and glutathione sulfonate. 5,5′-Dithio-bis-2-nitrobenzoate (DTNB) and l-cystine were also inhibitory, while dithiothreitol (DTT) and l-cysteine enhanced the K+-evoked release. Ten min preperfusion with 50 μM ZnCl2 enhanced the basal unstimulated release but prevented the activation of K+-evoked release by DTT.

Kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) evoked dopamine release but the other glutamate receptor agonists N-methyl-d-aspartate (NMDA), glycine (1 mM) and trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD, 0.5 mM), and the modulators GSH, GSSG, glutathione sulfonate, S-alkyl-derivatives of glutathione, DTNB, cystine, cysteine and DTT (all 1 mM) were without effect. The release evoked by 1 mM glutamate was enhanced by 1 mM GSH, while GSSG, glutathionesulfonate and S-alkyl derivatives of glutathione were generally without effect or inhibitory. NMDA (1 mM) evoked release only in the presence of 1 mM GSH but not with GSSG, other peptides or thiol modulators. l-Cysteine (1 mM) enhanced the glutamate-evoked release similarly to GSH. The activation by 1 mM kainate was inhibited by S-ethyl-, -propyl-, and -butylglutathione and the activation by 0.5 mM AMPA was inhibited by S-ethylglutathione but enhanced by GSSG.

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. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action, the γ-glutamyl and cysteinyl moieties of glutathione are involved.

Keywords

Dopamine releaseStriatal slicesGlutathioneGlutathione derivatives

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Réka Janáky
    • 1
  • Róbert Dohovics
    • 1
  • Pirjo Saransaari
    • 1
  • Simo S. Oja
    • 2
  1. 1.Brain Research CenterUniversity of Tampere Medical SchoolTampereFinland
  2. 2.The Centre for Laboratory MedicineTampere University HospitalTampereFinland