Modulation of brain mitochondrial membrane permeability and synaptosomal Ca2+ transport by dopamine oxidation

Effects of dopamine on the membrane permeability transition, thioredoxin re ductase activity, production of free radicals and oxidation of sulfhydryl g roups in brain mitochondria and the Ca2+ uptake by Na+-Ca2+ exchange and su lfhydryl oxidation in brain synaptosomes were examined. The brain mitochond rial swelling and the fall of transmembrane potential were altered by pretr eatment of dopamine in a dose dependent manner. Depressive effect of dopami ne on mitochondrial swelling was reversed by 10 mu g/ml catalase, and 10 mM DMSO. The activities of thioredoxin reductase in intact or disrupted mitoc hondria were decreased by dopamine (1-100 mu M), 25 mu M Zn2+ and 50 mu M M n2+. Dopamine-inhibited enzyme activity was reversed by 10 mu g/ml SOD and 10 mu g/ml catalase. Pretreatment of dopamine decreased Ca2+ transport in s ynaptosomes, which was restored by 10 mu g/ml SOD and 10 mM DMSO. Dopamine (1-100 mu M) in the medium containing mitochondria produced superoxide anio n and hydrogen peroxide, while its effect on nitrite production was very we ak. The oxidation of sulfhydryl groups in mitochondria and synaptosomes wer e enhanced by dopamine with increasing incubation times. Results suggest th at dopamine could modulate membrane permeability in mitochondria and calciu m transport at nerve terminals, which may be ascribed to the action of free radicals and the loss of reduced sulfhydryl groups.