Effect of the Hypoxanthine/Xanthine Oxidase System on Dopamine Outflow from Rat Striatal Synaptosomes

Abstract

The effect of the oxygen radical generating system, hypoxanthine/xanthine oxidase (Hx/XOD), on the spontaneous and potassium-stimulated outflow of the neurotransmitter dopamine (DA) from rat striatal synaptosomes was studied. The efficacy of some radical scavengers was also tested. DA outflow was measured by incubation of [³H]-DA prelabeled synaptosomes (P2) in Krebs-Ringer buffer, containing either normal or depolarizing K⁺ concentrations. The reactions were terminated by filtration of the synaptosomes through Sartorius filters.

Hx/XOD increased the spontaneous DA outflow in a dose and time dependent manner. The reduction found in synaptosomal DA content could be explained by disturbances of DA uptake or reuptake. The K⁺ stimulated outflow was not altered by the lower doses of Hx/XOD, whereas, when very high doses of Hx/XOD were used, the K⁺ stimulated DA outflow was decreased. High doses of Hx/ XOD may deplete the synaptosomal DA releasable pool, leaving little DA available for extra-stimulated outflow by high concentrations of K⁺. The K⁺-stimulated outflow of DA is a less sensitive process against radical attack than the spontaneous release of DA. A protective action of catalase, but no effect of superoxide dismutase was demonstrated in these experiments.

Abbreviations
DA, dopamine
Hx, hypoxanthine
XOD, xanthine oxidase
SOD, superoxide dismutase
NBT, nitroblue tetrazolium

Key words

Dopamine - Free radicals - Hypoxanthine - Hypoxia - Neurotransmitter - Xanthine oxidase