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 trans porter 2B (CAT-2B) and inducible nitric oxide synthetase (iNOS) in RAW 264 macrophages, which are thought to underlie the increased rate of a rginine uptake into these cells and its conversion to nitric oxide, re spectively. Here I demonstrate that the LPS- and IFN gamma-induced inc rease in arginine uptake into RAW263 cells is partially suppressed in the presence of PD 98059, partially suppressed in the presence of SE 2 03580, and completely inhibited by both drugs. In contrast, the LPS- a nd LFN gamma-induced synthesis of CAT-2B mRNA and iNOS protein is unaf fected by PD 98059 and SE 203580, The results indicate that the MAPK/E RK and SAPK2/p38 cascades are both rate-limiting for LPS- and IFN gamm a-stimulated arginine uptake, but not for iNOS synthesis. They also su ggest that PD 98059 and SE 203580 suppress CAT-2B synthesis at a post- transcriptional level. (C) 1998 Federation of European Biochemical Soc ieties.