Mechanisms and kinetics of citrulline uptake in a model of human intestinal epithelial cells

Background & aims: Citrulline is a major precursor of arginine by de novo synthesis in the kidneys. Oral. citrulline supplementation may be beneficial in some clinical. conditions. However, citrulline bioavailability depends on its intestinal absorption. Since the mechanism of citrulline transport across the intestine has not been established yet, this study was designed to characterize L-[C-14]-citrulline uptake by Caco-2 cells. Methods: Caco-2 cells were cultured in a bicameral insert system. Inhibition studies were conducted in the presence of neutral, cationic, acidic and non-metabolized amino acids. We performed control inhibition studies for arginine uptake. Results: Citrulline uptake was pH-independent whereas the uptake rate was reduced in the absence of Na+. Kinetic analysis indicated the involvement of Na+-dependent and Na+-independent saturable transport components. For competition studies, both the transport components were markedly inhibited by large, small neutral and cationic amino acids. It was also noticed that specific inhibitor of system LBCH inhibited uptake. The inhibition profile of arginine transport was different from that of citrulline transport as arginine uptake was insensitive to BCH. Conclusions: These characteristics suggest that system B-0,B-+ might be responsible for the Na+-dependent uptake of citrulline, whereas Na+-independent uptake may include systems L and b(0,+). Our results show that systems involved in citrulline transport are partly different from those involved in arginine transport. (C) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. Ail rights reserved.