Nitric oxide-induced nitration of catecholamine neurotransmitters: a key to neuronal degeneration?

Exposure of the neurotransmitters dopamine (1a) and norepinephrine (1b), as well as of other catechol compounds (1c-e), to nitric oxide (NO) in aerated phosphate buffer at room temperature leads to the corresponding 6-nitroderivatives (2a-e) in yields higher than 80%. Formation of nitration products depends on the presence of oxygen and is inhibited by excess ascorbic acid, whereas sulfhydryl compounds, e.g. cysteine, and scavengers of reactive oxygen species, such as catalase and superoxide dismutase, exert no significant inhibitory effect. O-Methylated catechols are poorly or not reactive toward NO. These and other observations are consistent with a mechanism involving coupling of a semiquinone radical with NO or a higher oxide, e.g. nitrogen dioxide (NO2). The observed formation of potentially toxic 6-nitrocatecholamines under physiologically relevant conditions may open new perspectives to an understanding of the biochemical processes underlying NO-induced toxicity and neuronal degeneration.