Effect of the hypoxanthine/xanthine oxidase system on dopamine outflow from rat striatal synaptosomes

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.