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

Exposure of the neurotransmitters dopamine and norepinephrine , as well as of other catechol compds., to nitric oxide (NO) in aerated phosphate buffer at room temp. leads to the corresponding 6-nitro derivs. in yields higher than 80%. Formation of nitration products depends on the presence of oxygen and is inhibited by excess ascorbic acid, whereas sulfhydryl compds., 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 obsd. formation of potentially toxic 6-nitro catecholamines under physiol. relevant conditions may open new perspectives to an understanding of the biochem. processes underlying NO-induced toxicity and neuronal degeneration.