Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, bioc hemical and neuropathologic changes reminiscent of those which occur in idi opathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selecti ve inhibitor of the neuronal isoform of nitric oxide synthase. We previousl y demonstrated that administration of 7-NI is effective in blocking MPTP to xicity in both mice and baboons. This was suggested to be due to inhibition of the generation of peroxynitrite which can nitrate tyrosines. In the pre sent study we found increased 3-nitrotyrosine immunoreactivity in the subst antia nigra of MPTP treated baboons, which was blocked by coadministration of 7-NI. These findings provide further evidence that peroxynitrite may pla y a role in MPTP induced parkinsonism in baboons. (C) 1999 Elsevier Science B.V. All rights reserved.