DIFFERENTIAL SENSITIVITY TO HYDROGEN-PEROXIDE OF DOPAMINERGIC AND NORADRENERGIC NEUROTRANSMISSION IN RAT-BRAIN SLICES

Citation
Ch. Langeveld et al., DIFFERENTIAL SENSITIVITY TO HYDROGEN-PEROXIDE OF DOPAMINERGIC AND NORADRENERGIC NEUROTRANSMISSION IN RAT-BRAIN SLICES, Free radical biology & medicine, 19(2), 1995, pp. 209-217
Citations number
47
Categorie Soggetti
Biology
ISSN journal
08915849
Volume
19
Issue
2
Year of publication
1995
Pages
209 - 217
Database
ISI
SICI code
0891-5849(1995)19:2<209:DSTHOD>2.0.ZU;2-1
Abstract
Oxidative stress, induced by hydrogen peroxide, has been implicated in the pathogenesis of Parkinson's disease. Only scarce information is a vailable if and how hydrogen peroxide, a side product of catecholamine (CA) breakdown, interferes with CAergic neurotransmission. Therefore, we investigated the effect of hydrogen peroxide on the release of [H- 3]dopamine (DA) and [H-3]noradrenaline (NA) from rat striatal and cort ical tissue slices, respectively. Hydrogen peroxide (0.01-1 mM) stimul ated the spontaneous release of [H-3]DA from striatal slices. Its effe ct on [H-3]NA release from cortical slices, however, was much smaller than on DA release and occurred only in concentrations above 0.1 mM. F urthermore, only in concentrations of 1 mM or higher did a stimulation of spontaneous release of radioactivity from striatal slices incubate d with [H-3]choline occur. Omission of calcium significantly enhanced the effect on DA release, and an increase of calcium significantly red uced it. Blockade of vesicular storage with reserpine (0.3 mu M) almos t completely abolished [H-3]DA release induced by hydrogen peroxide. F ollowing incubation of striatal slices with [H-3]NA in the presence of the NA (re)uptake blocker desmethylimipramine (0.3 mu M), NA release was observed at a concentration (0.1 mM) at which no effect occurred i n cortical slices. Moreover, under these conditions [(3)]NA and [H-3]D A release from striatal slices reached comparable levels. Our results show that hydrogen peroxide induces a nonexocytotic release of DA and NA by interfering with the vesicular uptake and/or storage of these CA s. However, the striatal DA storage system, irrespective of the presen ce of either DA or NA, appeared to be substantially more sensitive to this effect than its cortical equivalent for storage of NA.