Specific reversible stimulation of system y(+) L-arginine transport activity in human intestinal cells

L-Arginine, which is intimately involved in cellular immune functions and nitric oxide biology, is transported by intestinal cells largely via transport System y(+). The gut epithelium is exposed to various luminal amino acids at any given time, and therefore the purpose of this study was to study the regulation of luminal arginine transport by other amino acids. System y(+) L-arginine transport activity was measured in Caco-2 monolayers exposed to various amino acids. L-arginine and/or other System y(+) substrates specifically upregulated System y(+) transport activity twofold after 1 hour, with a response noted as early as 5 minutes. Non-System y(+) substrates did not affect L-arginine absorption. Kinetic analysis indicated that L-arginine exposure increased both System y(+) K(m) and V(max). Neither cycloheximide nor actinomycin affected this stimulation, indicating that the regulation did not involve transcription or translation. The System y(+) substrate activation effect was reversible. L-arginine transport activity returned to baseline within 3 hours when cells were reincubated in amino acid-free media. These data indicate that System y(+) arginine transport activity is rapidly and reversibly activated by System y(+) substrates via a mechanism consistent with transmembrane stimulation. These findings identify a mechanism by which luminal nutrients regulate arginine uptake by the gut.