Glutaminergic tonic action potentiate MPP⁺-induced hydroxyl radical production in rat striatum

The effect of glycine on 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced hydroxyl radical (OH) formation in the extracellular fluid of rat striatum were investigated. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/μl/min) was infused through a microdialysis probe to detect the generation of OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA) in rat striatum. MPP⁺ (5 mmol/L) produced an increase in OH formation. When glycine (1 mmol/L) was infused into the rat striatum through a microdialysis probe after MPP⁺ treatment, the marked in the level of 2,3-DHBA was observed in the brain dialysate. However, in the presence of MK-801 (100 μmol/L), a non competitive antagonist of N-methyl-D-aspartate (NMDA), glycine failed to increase the 2,3-DHBA formation by MPP⁺. When corresponding experiments were performed with nitro-L arginine (L-NNA) (1 mmol/L), a nitric oxide synthase (NOS) inhibitor, same result was obtained. These results suggest that MPP⁺-induced OH generation may modulated by glycine via NMDA receptor in rat striatum. This increase might be explained because of the presence of a glutaminergic tonic action.