Dopamine enhances mtNOS activity: Implications in mitochondrial function

Dopamine and nitric oxide systems can interact in different processes in the central nervous system. Dopamine and oxidation products have been related to mitochondrial dysfunction. In the present study, intact mitochondria and submitochondrial membranes were incubated with different DA concentrations for 5 min. Dopamine (1 mM) increased nitric oxide production in submitochondrial membranes and this effect was partially prevented in the presence of both DA and NOS inhibitor Nω-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 dopamine 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 mainly due to its metabolism by MAO. Also, DA-induced depolarization was prevented by the addition of l-NNA showing the involvement of nitric oxide in this process too. This work provides evidence that in the studied conditions, dopamine modifies mitochondrial function by a nitric oxide-dependent pathway.