The effect of inflammatory stimuli on NMDA-related activation of glutamine synthase in human cultured astroglial cells

Incubation of human cultured astroglial cells with NMDA (100 μM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since l-NAME (500 μM), an inhibitor of NO synthase, reversed this effect. NMDA-related increase of GS activity and glutamine concentration was antagonised by previous incubation of astroglial cells with a mixture of LPS plus γIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus γIFN inhibit elevation of GS activity subsequent to NMDA receptor stimulation in astroglial cells via enhancement of inducible NO synthase, and this may represent the site of interaction between pro-inflammatory and excitotoxic stimuli in the brain.