Modulation of [3H]dopamine release by glutathione in mouse striatal slices.

Réka Janáky, Róbert Dohovics, Pirjo Saransaari, Simo S Oja

文献索引：Neurochem. Res. 32 , 1357-1364, (2007)

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摘要

Glutathione (gamma-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 [(3)H]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 microM ZnCl(2) 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 Ca(2+ )channels. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action, the gamma-glutamyl and cysteinyl moieties of glutathione are involved.