Transport of L-arginine in arginine-deprived endothelial cells

In vascular endothelium, L-arginine (ARG) plays a crucial role as a substrate for various metabolic pathways, one of which is the synthesis of bioregulatory nitric oxide. Transport of ARG across the cell membrane determines intracellular substrate availability. Membranous transport in turn may be dependent on the extra-to-intracellular gradient in ARG concentration. To test this hypothesis ARG transport was characterized in control and ARG-deprived endothelial cells (EC). Within a two-hour deprivation period a decrease of more than 50% in intracellular ARG concentration was observed. Initial uptake rates for ARG revealed no significant differences between ARG-deprived and control EC (30.0 +/- 2.7 vs. 30.6 +/- 2.1 pmol*(mg protein*min)-1). Two distinct ARG transporter components were observed dependent on extracellular ARG concentration. No significant differences between ARG-deprived and control EC were found with respect to the kinetics of these ARG transporter components. The present data suggest that in this model the transport rate of ARG into EC is not directly dependent on the intracellular ARG concentration. Thus, a feedback loop between intracellular ARG concentration and ARG transporters as a critical determinant for endothelial ARG-dependent pathways such as NO-synthesis appears highly unlikely.