Activated macrophages require L-arginine uptake to sustain NO synthesis. Several transport systems could mediate this L-arginine influx. Using competition analysis and gene-expression studies, amino acid transport system y+ was identified as the major carrier responsible for this activity. To identify which of the four known y+ transport-system genes is involved in macrophage-induced L-arginine uptake, we used a hybrid-depletion study in Xenopus oocytes. Cationic amino acid transporter (CAT) 2 antisense oligodeoxyribonucleotides abolished the activated-macrophage-mRNA-induced L-arginine transport. Together with expression studies documenting that CAT2 mRNA and protein levels are elevated with increased L-arginine uptake, our data demonstrate that CAT2 mediates the L-arginine transport that is required for the raised NO production in activated J774 macrophages.
CAT2-mediated l-arginine transport and nitric oxide production in activated macrophages
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Donald K. KAKUDA, Matthew J. SWEET, Carol L. MACLEOD, David A. HUME, Daniel MARKOVICH; CAT2-mediated l-arginine transport and nitric oxide production in activated macrophages. Biochem J 1 June 1999; 340 (2): 549–553. doi: https://doi.org/10.1042/bj3400549
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