Stimulation of Arginine Transport and Nitric Oxide Production by Lipopolysaccharide Is Mediated by Different Signaling Pathways in Astrocytes

Abstract

Transport of L-arginine and generation of nitrite in microglia-free astroglial cultures derived from neonatal mouse brain were stimulated by bacterial lipopolysaccharide (LPS) in a time- and dose-dependent manner. LPS stimulated arginine transport between 1.3- and 2.5-fold; half-maximal stimulation was obtained with 0.3 micrograms/ml LPS. Acceleration of transport was detectable within 6 h of incubation with LPS. Cycloheximide or actinomycin D neutralized the effect of LPS. Stimulation of generation of nitrite was reduced when the cells were incubated simultaneously with LPS and either genistein or diethyldithiocarbamate, inhibitors of protein tyrosine kinase and nuclear transcription factor kappa, respectively. However, stimulation of arginine transport was not reduced in the presence of these compounds. Dexamethasone inhibited stimulation of nitric oxide (NO) production but not of arginine transport. Protein kinase C inhibitor staurosporine had no effect on either process. The results suggest that LPS-stimulated acceleration of arginine transport in astrocytes requires protein as well as RNA synthesis. Induction of synthesis of an astroglial cationic amino acid transport system appears to be mechanistically independent from stimulation of intracellular NO production.