A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the "arginine paradox".
Immunohistochemistry of porcine pulmonary artery endothelial cells (PAEC) with antibodies specific for caveolin, endothelial nitric-oxide synthase (eNOS), and the arginine transporter (CAT1) demonstrates that all of these proteins co-localize in plasma membrane caveolae. When incubated with solubilized PAEC plasma membrane proteins, eNOS-specific antibody immunoprecipitates CAT1-mediated arginine transport. These results document the existence of a caveolar complex between CAT1 and eNOS in PAEC that provides a mechanism for the directed delivery of substrate arginine to eNOS. Direct transfer of extracellular arginine to membrane-bound eNOS accounts for the "arginine paradox" and explains why caveolar localization of eNOS is required for optimal nitric oxide production by endothelial cells.
McDonald
K K
KK
Department of Biochemistry and Molecular Biology and the Center for Structural Biology, University of Florida College of Medicine, Gainesville, Florida 32610-0245, USA.
Zharikov
S
S
Block
E R
ER
Kilberg
M S
MS
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000502:physiology*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D013552:Swine
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D051242:Caveolin 1; D022461:Caveolins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D001120:Arginine; D019001:Nitric Oxide Synthase