STIMULATION OF ARGININE TRANSPORT AND NITRIC-OXIDE PRODUCTION BY LIPOPOLYSACCHARIDE IS MEDIATED BY DIFFERENT SIGNALING PATHWAYS IN ASTROCYTES

Transport of L-arginine and generation of nitrite in microglia-free as troglial cultures derived from neonatal mouse brain were stimulated by bacterial lipopolysaccharide (LPS) in a time- and dose-dependent mann er. LPS stimulated arginine transport between 1.3- and 2.5-fold; half- maximal stimulation was obtained with 0.3 mu g/ml LPS. Acceleration of transport was detectable within 6 h of incubation with LPS. Cyclohexi mide or actinomycin D neutralized the effect of LPS. Stimulation of ge neration of nitrite was reduced when the cells were incubated simultan eously with LPS and either genistein or diethyldithiocarbamate, inhibi tors of protein tyrosine kinase and nuclear transcription factor kappa , respectively. However, stimulation of arginine transport was not red uced in the presence of these compounds. Dexamethasone inhibited stimu lation of nitric oxide (NO) production but not of arginine transport. Protein kinase C inhibitor staurosporine had no effect on either proce ss. The results suggest that LPS-stimulated acceleration of arginine t ransport in astrocytes requires protein as well as RNA synthesis. Indu ction of synthesis of an astroglial cationic amino acid transport syst em appears to be mechanistically independent from stimulation of intra cellular NO production.