Effect of L-arginine/nitric oxide pathway on MPP(+)-induced cell injury in the striatum of rats.
1. Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, N omega-nitro-L-arginine (L-NOARG) and L-arginine, was studied in the corpus striatum by means of two MPP+ perfusions separated by 24 h. Dopamine extracellular output after the second MPP+ (1, 5 and 10 mM) perfusion was considered as an index of the dopaminergic neurone damage produced by the first MPP+ (1, 5 and 10 mM) perfusion. 2. L-NOARG, systemically administered (10 mg kg-1, i.p., every 12 h for 4 days), failed to prevent the neurotoxic action of MPP+ (1 and 10 mM). On the contrary, the neurotoxic effect of MPP+ was increased by L-NOARG administration. 3. L-Arginine (10 mM) perfused 2 h before MPP+ perfusion did not protect against the neurotoxic action of high MPP+ concentrations (5 and 10 mM). At the highest MPP+ concentration used (10 mM), the increase in the extracellular output of dopamine after the second MPP+ perfusion was slower in L-arginine-treated rats than in control and L-NOARG-treated rats. 4. When MPP+ (1 mM) was perfused 2 h after L-arginine (10 mM) perfusion, there was a clear protection against MPP+ neurotoxicity. In the second MPP+ (1 mM) perfusion, the increase in the extracellular output of dopamine in L-arginine-treated rats was twice as high as for the control rats. 5. The results indicate that NO may exert a protective mechanism in the presence of a low ambient redox.
Santiago
M
M
Departamento de Bioquímica, Facultad de Farmacia, Sevilla, Spain.
Machado
A
A
Cano
J
J
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use*; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine