Selective targeting of nitric oxide synthase inhibitors to system y+ in activated macrophages

Original article can be found at: http://www.sciencedirect.com/science/journal/0006291X Copyright Elsevier Inc. DOI : 10.1006/bbrc.1994.1511Amino acid transport systems mediating uptake of nitric oxide (NO) synthase inhibitors were characterized in the murine macrophage cell line J774. Treatment of J774 cells with bacterial endotoxin (LPS, 1 μg ml-1, 24 h) selectively increased the transport capacity for NG-monomethyl-L-[14C]arginine (L-NMMA), whereas transport of NG-nitro-L-[3H]arginine (LNNA) was unaffected. Inhibition studies established that the cationic transport system y+ mediates uptake of L-arginine, L-NMMA and NG-iminoethyl-L-ornithine (L-NIO). A neutral transporter, with low substrate specificity and insensitive to LPS, mediates uptake of L-citrulline, L-NNA and its methyl ester L-NAME. We conclude that enhanced expression of the y+ transporter in LPS-stimulated macrophages (1) may facilitate the targeting of selective inhibitors of inducible NO synthase to activated cells generating NO in endotoxin shock.Peer reviewe