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
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.