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, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase. We previously demonstrated that administration of 7-NI is effective in blocking MPTP toxicity in both mice and baboons. This was suggested to be due to inhibition of the generation of peroxynitrite which can nitrate tyrosines. In the present study we found increased 3-nitrotyrosine immunoreactivity in the substantia nigra of MPTP treated baboons, which was blocked by coadministration of 7-NI. These findings provide further evidence that peroxynitrite may play a role in MPTP induced parkinsonism in baboons.
Ferrante
R J
RJ
Neurology, Pathology, and Psychiatry Departments, Boston University School of Medicine, Boston, MA, USA.
Hantraye
P
P
Brouillet
E
E
Beal
M F
MF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010215:Papio; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; C002744:3-nitrotyrosine; D014443:Tyrosine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole