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 (PA EC) with antibodies specific for caveolin, endothelial nitric-oxide sy nthase (eNOS), and the arginine transporter (CAT1) demonstrates that a ll of these proteins co-localize in plasma membrane caveolae. When inc ubated with solubilized PAEC plasma membrane proteins, eNOS-specific a ntibody immunoprecipitates CAT1-mediated arginine transport. These res ults document the existence of a caveolar complex between CAT1 and eNO S in PAEC that provides a mechanism for the directed delivery of subst rate arginine to eNOS. Direct transfer of extracellular arginine to me mbrane-bound eNOS accounts for the ''arginine paradox'' and explains w hy caveolar localization of eNOS is required for optimal nitric oxide production by endothelial cells.