Search PubMedSearch

Biomedical subjects

F Girbe

Publications and source records attributed to F Girbe.

4 recordsLinked to original sources

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).

Analysis of Variance

Ascorbic acid increases synaptosomal potassium-induced dopamine release.

On synaptosomes prepared from striata of mice, increasing concentrations of ascorbic acid (from 0.01 mM to 0.5 mM) did not modify the 3H-dopamine uptake. However, at the 0.1 mM concentration, ascorbic acid increased the potassium-induced release of 3H-dopamine by synaptosomes previously loaded with the amine. This effect was dependent on the presence of Ca2+ in the superfusion medium and was not shared by dehydroascorbic acid (from 1 mM to 0.01 mM). This effect of ascorbic acid, which occurs in the range of its endogenous concentrations, suggests that it is a putative modulator of dopaminergic transmission.

Animals

Ginkgo biloba extract EGb 761 or trolox C prevent the ascorbic acid/Fe2+ induced decrease in synaptosomal membrane fluidity.

The ability of synaptosomes, prepared from striata, to take up 3H-dopamine declined rapidly during incubation at 37 degrees C, in an oxygenated Krebs-Ringer medium with 0.1 mM ascorbic acid. Ascorbic acid was responsible for this decrease. Its effectiveness after a 60 min incubation was concentration dependent from 1 microM and virtually complete for 0.1 mM. Furthermore, a decrease of synaptosomal membrane fluidity was revealed by measurements of fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene. This decrease was potentiated by Fe2+ ions (1 microM). In contrast, it was prevented by the Fe2+ ion chelator, desferrioxamine (0.1 mM), by the Ginkgo biloba extract EGb 761 [2-16 micrograms/ml], as well as by the flavonoid quercetin (0.1 microM). This preventive effect was shared by trolox C (from 0.1 mM). It is concluded that peroxidation of neuronal membrane lipids induced by ascorbic acid/Fe2+ is associated with a decrease in membrane fluidity which, in turn, reduces the ability of the dopamine transporter to take up dopamine.

Animals