Peroxidation of synaptosomes alters the dopamine uptake complex but spares the exocytotic release of dopamine.
Synaptosomes, prepared from the striata of mice, and incubated for 1 h in a Krebs-Ringer medium with the peroxidative combination of ascorbic acid (0.1 mM)/Fe2+ (1 microM), lose their ability to take up [3H] dopamine. This effect is associated with a decrease in binding of the dopamine uptake inhibitor [3H] GBR 12783. The free radical scavenger trolox C (0.1 mM) and the Ginkgo biloba extract EGb 761 (10 micrograms/ml) prevent both effects. Although submitted to these peroxidative conditions after loading with [3H] DA, superfused synaptosomes retain their ability to release [3H] DA when depolarized by high potassium concentrations (40 mM). This release is higher than that observed when synaptosomes are incubated without ascorbic acid/Fe2+, and does not seem to depend upon peroxidation, since it is also observed when incubation is performed in the presence of the free radical scavengers EGb 761 (10 micrograms/ml) and trolox C (0.1 mM).