Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW264 macrophages

Bacterial lipopolysaccharide (LPS) in the presence of interferon gamma (IFN gamma) stimulates the synthesis of the cationic amino acid transporter 2B (CAT-2B) and inducible nitric oxide synthetase (iNOS) in RAW264 macrophages, which are thought to underlie the increased rate of arginine uptake into these cells and its conversion to nitric oxide, respectively. Here I demonstrate that the LPS- and IFN gamma-induced increase in arginine uptake into RAW263 cells is partially suppressed in the presence of PD 98059, partially suppressed in the presence of SE 203580, and completely inhibited by both drugs. In contrast, the LPS- and LFN gamma-induced synthesis of CAT-2B mRNA and iNOS protein is unaffected by PD 98059 and SE 203580, The results indicate that the MAPK/ERK and SAPK2/p38 cascades are both rate-limiting for LPS- and IFN gamma-stimulated arginine uptake, but not for iNOS synthesis. They also suggest that PD 98059 and SE 203580 suppress CAT-2B synthesis at a post-transcriptional level. (C) 1998 Federation of European Biochemical Societies.