A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the 'arginine paradox'

Abstract

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.