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

FEBS Lett. 1998 Jun 16;429(3):249-53. doi: 10.1016/s0014-5793(98)00578-x.


Bacterial lipopolysaccharide (LPS) in the presence of interferon gamma (IFNgamma) 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 IFNgamma-induced increase in arginine uptake into RAW264 cells is partially suppressed in the presence of PD 98059, partially suppressed in the presence of SB 203580, and completely inhibited by both drugs. In contrast, the LPS- and IFNgamma-induced synthesis of CAT-2B mRNA and iNOS protein is unaffected by PD 98059 and SB 203580. The results indicate that the MAPK/ERK and SAPK2/p38 cascades are both rate-limiting for LPS- and IFNgamma-stimulated arginine uptake, but not for iNOS synthesis. They also suggest that PD 98059 and SB 203580 suppress CAT-2B synthesis at a post-transcriptional level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Basic
  • Animals
  • Arginine / metabolism*
  • Biological Transport
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carrier Proteins / biosynthesis*
  • Enzyme Activation / drug effects
  • Flavonoids / pharmacology
  • Imidazoles / pharmacology
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism*
  • Membrane Proteins / biosynthesis*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Pyridines / pharmacology
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases


  • Amino Acid Transport Systems, Basic
  • Carrier Proteins
  • Flavonoids
  • Imidazoles
  • Lipopolysaccharides
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Pyridines
  • Interferon-gamma
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one