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.