Dopamine modulates mitochondrial function. Involvement of nitric oxide

CZERNICZYNIEC, A.; BUSTAMANTE, J.; LORES ARNAIZ, S.

Pinamar, Buenos Aires, Argentina

Congreso; X Congreso Panamerican Association for Biochemistry and Molecular Biology, XLI Reunión Annual Sociedad Argentina de Investigación Bioquímica, XX Reunión Anual Sociedad Argentina de Neuroquímica; 2005

Panamerican Association for Biochemistry and Molecular Biology, Sociedad Argentina de Investigación Bioquímica, Sociedad Argentina de Neuroquímica

Dopamine is able to induce neurotoxic effects in several neurological and psychiatrics diseases. It has been postulated that dopamine may generate changes on mitochondrial function by inhibition of respiratory chain. The aim of this work was to determine the in vitro effects of dopamine on mitochondrial function and the possible involvement of nitric oxide (NO). Mouse brain mitochondria were isolated by differential centrifugation. Further mitochondrial purification was performed by Ficoll gradient. Mitochondrial function was evaluated through the measurements of: a) O2 consumption in intact mitochondria and b) respiratory complexes activity in submitochondrial particles (SMP). No significant changes in O2 consumption in state 4 were observed after dopamine incubation. Dopamine (5-10-15 mM) inhibited state 3 O2 consumption in brain mitochondria by 19, 28 and 46% respectively. When mitochondria were incubated with 15 mM dopamine in the presence of the NOS inhibitor L-NNA (0.5 mM), state 3 respiratory rate was decreased by only 17%, showing that NO may play a role in respiratory chain inhibition by dopamine. Incubation of SMP with 1mM dopamine inhibited complex I activity by 20%. Complex IV was significantly inhibited by incubation of SMP with 1 mM dopamine, and the effect was partially prevented by L-NNA. Our results show that NO is involved in the mechanism of inhibition of the respiratory chain by dopamine.