Effect of l‐arginine/nitric oxide pathway on MPP⁺‐induced cell injury in the striatum of rats

Abstract

1 Protection against 1-methyl-4-phenylpyridinium ion (MPP+) neurotoxicity by two nitric oxide-related compounds, Nw-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-', 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.

Lipopolysaccharide Intranigral Injection Induces Inflammatory Reaction and Damage in Nigrostriatal Dopaminergic System

“…The fact that our study was performed in vivo could be a reason for the discrepancy. However, our finding is in accor-dance with that described previously by our group (Santiago et al, 1994), where inhibition of NO production did not protect the dopaminergic system against MPP~damage, and with previous work by Sawada et al (1996), who found that NO-generating agents showed neurotoxic effects restricted exclusively to nondopaminergic neurons (Sawada et al, 1996). All these data suggest that in our model the dopaminergic neurotoxicity is not mediated by NO.…”

Nigral and Striatal Comparative Study of the Neurotoxic Action of 1‐Methyl‐4‐Phenylpyridinium Ion: Involvement of Dopamine Uptake System

“…Perfusion of MPP + (1, 2.5, and 5 mM) in the substantia nigra for 15 mm produced a marked and dose-dependent increase in the extracellular output of DA, indicative of its neurotoxic action (Santiago et al, 1991). In contrast, in the striatum the first MPP + perfusion produced a maximal output of DA that was similar for the two doses applied, a result also found with MPP~(10 mM) assayed in a previous report (Santiago et al, 1994). Another difference found between substantia nigra and striatum was that, in the former, the increase in the output of DA was similar at the first and second MPP~(1 mM) perfusion.…”

Brain Nitric Oxide and Its Dual Role in Neurodegeneration / Neuroprotection: Understanding Molecular Mechanisms to Devise Drug Approaches

“…It was further demonstrated that nNOS deficient mutant mice are resistant to MPTP, suggesting that neuronally derived NO might be involved in the neurotoxic action [205]. However, NO protects dopaminergic neurons and cultured rat astrocytes from MPP+ induced toxicity [425,426] and erythropoietin is protective in (MPTP)-induced mouse model of Parkinson's disease via increasing NO production [427].…”