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

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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.

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Acknowledgments

The skilful technical assistance of Ms Oili Pääkkönen, Ms. Irma Rantamaa and Ms Sari Luokkala is gratefully acknowledged. The study was financially supported by the competitive research funding of Pirkanmaa Hospital District.

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Authors and Affiliations

  1. Brain Research Center, University of Tampere Medical School, Tampere, Finland

    Réka Janáky, Róbert Dohovics & Pirjo Saransaari

  2. The Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland

    Simo S. Oja

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  1. Réka Janáky
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Correspondence to Simo S. Oja.

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Janáky, R., Dohovics, R., Saransaari, P. et al. Modulation of [3H]Dopamine Release by Glutathione in Mouse Striatal Slices. Neurochem Res 32, 1357–1364 (2007). https://doi.org/10.1007/s11064-007-9315-z

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