CAT2-mediated L-arginine transport and nitric oxide production in activated macrophages.
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.
Kakuda
D K
DK
Department of Physiology and Pharmacology, University of Queensland, Brisbane 4072, Australia.
Sweet
M J
MJ
Mac Leod
C L
CL
Hume
D A
DA
Markovich
D
D
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
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine