Opposite effects of low and high doses of arginine on glutamate-induced nitric oxide formation in rat substantia nigra.

L-arginine is a very versatile amino acid that is involved in many important physiological processes such as protein, nitric oxide (NO), agmatine, putrescine, urea, L-ornithine or creatine synthesis and is essential for posttranslational arginylation of protein. The present study was designed to evaluate in vivo the effect of L-arginine on NO production in substantia nigra. In vivo spectroscopic and voltammetric studies were addressed in rats to record modifications in methemoglobin and NO levels under glutamate stimulation. Results showed that, under physiological L-arginine extracellular concentration, the intranigral infusion of glutamate produced an increase in NO levels. When a low dose of L-arginine was co-infused with glutamate, a persistent and higher increase in NO levels was observed. The co-infusion of glutamate with a moderate dose of L-arginine induced drastic and persistent NO production. It was also observed that high doses of either L-arginine or D-arginine inhibit NO production. Subsequently, these data show that L-arginine and D-arginine are involved in a mechanism that inhibits NO production.