title: CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, Australia.
authors.forename: D K
authors.initials: DK
authors.lastname: Kakuda
authors.forename: M J
authors.initials: MJ
authors.lastname: Sweet
authors.forename: C L
authors.initials: CL
authors.lastname: Mac Leod
authors.forename: D A
authors.initials: DA
authors.lastname: Hume
authors.forename: D
authors.initials: D
authors.lastname: Markovich
mesh_terms: D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine