TRANSPORT OF L-ARGININE IN ARGININE-DEPRIVED ENDOTHELIAL-CELLS

In vascular endothelium, L-arginine (ARG) plays a crucial role as a su bstrate for various metabolic pathways, one of which is the synthesis of bioregulatory nitric oxide. Transport of ARG across the cell membra ne determines intracellular substrate availability Membranous transpor t in turn may be dependent on the extra-to-intracellular gradient in A RG concentration. To test this hypothesis ARG transport was characteri zed in control and ARG-deprived endothelial cells (EC). Within a two-h our deprivation period a decrease of more than 50% in intracellular AR G 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 transpo rter components were observed dependent on extracellular ARG concentra tion. No significant differences between ARG-deprived and control EC w ere found with respect to the kinetics of these ARG transporter compon ents. The present data suggest that in this model the transport rate o f ARG into EC is not directly dependent on the intracellular ARG conce ntration. Thus, a feedback loop between intracellular ARG concentratio n and ARG transporters as a critical determinant for endothelial ARG-d ependent pathways such as NO-synthesis appears highly unlikely. (C) 19 95 Academic Press, Inc.