P1,P4-Diadenosine 5′-Tetraphosphate Modulates l-Arginine and l-Citrulline Uptake by Bovine Aortic Endothelial Cells

We have previously demonstrated that P1,P4-diadenosine 5′-tetraphosphate (Ap4A) interacts with high-affinity and low-affinity binding sites on the bovine aortic endothelial cell (BAEC) surface. In this report we demonstrate that Ap4A interaction with the lower affinity site modulates l-arginine (l-Arg) and l-citrulline (l-Cit) uptake by BAEC. Competition uptake studies demonstrate that l-Arg and l-Cit uptake occurs through a common transporter system that is sensitive to Ap4A. Evidence is also presented that is consistent with Ap4A modulating l-Arg uptake by increasing the affinity of l-Arg for the transporter.