Dopamine induces mitochondrial dysfunction mainly by a NO-dependent pathway.

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

Montevideo, Uruguay

Congreso; V Meeting of SFRBM – South American Group, V International Conference on Peroxynitrite and Reactive Nitrogen Species; 2007

Society for Free Radical Biology and Medicine

Dopamine (DA) and nitric oxide (NO) systems can interact in different processes in the central nervous system. Dopamine and oxidation products have been related to  mitochondrial dysfunction. The aim of this study was to evaluate if DA is able to modify mitochondrial function by a mechanism which involves NO production. Intact mitochondria and submitochondrial particles (SMP) were incubated with different DA concentrations for 5 minutes. Dopamine (1 mM) increased NO production in SMP and this effect was partially prevented in the presence of both DA and NOS inhibitor Nw-nitro-L-arginine (L-NNA). A 46% decrease in state 3 oxygen uptake (active respiration state) was found after 15 mM dopamine incubation. When mitochondria were incubated with 15 mM DA in the presence of L-NNA, state 3 respiratory rate was decreased by only 17% showing the involvement of NO. As shown for O2 consumption, the inhibition of cytochrome oxidase by 1 mM DA was mediated by NO. Hydrogen peroxide production significantly increased after 15 mM DA incubation, being 68% due to its metabolism by MAO and 19% due to the increase in NO production. Also, DA-induced depolarization was prevented by the addition of L-NNA showing the involvement of NO in this process too. This work provides evidence that in our study conditions, DA modifies mitochondrial function by a NO-dependent pathway.