Altered nitric oxide production in mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin or methamphetamine.
Several studies have demonstrated the involvement of reactive nitrogen and oxygen species (RNOS) in the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin (MPTP) and methamphetamine (METH), so the contribution of altered nitric oxide synthase (NOS) enzyme function can be suspected. In this study, about 50% increase in nitric oxide (NO) production in the mouse striatum was found between 4 and 12 h after a single MPTP injection, allowing an increased peroxynitrite (ONOO-) formation in the target brain region. However, METH injection induced a rapid decrease of NO formation both in mouse striatum and hippocampus, reaching its minimum level at 2 h, and restored to the control value after 6 h in the striatum and 12 h in the hippocampus. The uncoupled function of NOS with increased superoxide (O2*-) production after METH injection is suggested.
Halász
A S
AS
Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary. halatt@net.sote.hu
Pálfi
M
M
Tábi
T
T
Magyar
K
K
Szöko
E
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D015259:Dopamine Agents / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I; D030421:Peroxynitrous Acid / Q000378:metabolism
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D008694:Methamphetamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse