Immunostimulation of rat primary astrocytes decreases intracellular ATP level

in this study we investigated the effect of immunostimulation on intracellu lar ATP level in rat glial cells. Rat primary astrocytes or C6 glioma cells were treated for 48 h with IFN-gamma, LPS or IFN-gamma plus LPS. These tre atments increased NO production from the cells and a synergistic increase i n NO production was observed with IFN-gamma plus LPS. Intracellular ATP lev el was decreased to about half the control level at the highest concentrati on of IFN-gamma (100 U/ml) plus LPS (1 mug/ml) without affecting cell viabi lity. The level of intracellular ATP was inversely correlated with the exte nt of NO production from the glial cells. The increase in NO production is at least 6 h ahead of the initiation of ATP depletion, and NOS inhibitor N- G-nitro-L-arginine (NNA) or N omega -nitro-L-arginine methyl ester (L-NAME) inhibited NO production and ATP depletion. Exogenous addition of peroxynit rite generator 3-morpholinosydnonimine (SLN-1) and to a lesser extent NO ge nerator S-nitroso-N-acetylpenicillamine (SNAP) depleted intracellular ATP l evel in a dose-dependent manner. The results from the present study imply t hat immunostimulation of rat glial cells decreases the intracellular ATP le vel without affecting cell viability. Considering the role of astrocytes as an essential regulator of the extracellular environment in the brain, the immunostimulation-induced decrease in intracellular ATP level may participa te in the pathogenesis of various neurological diseases. (C) 2001 Elsevier Science B.V. All rights reserved.