Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b0,+AT-rBAT (SLC7A9-SLC3A1)

L-arginine and its (patho-)physiologically active derivatives, L-homoarginine and asymmetric dimethylarginine (ADMA), show significant differences in their renal clearance. The underlying molecular mechanisms remain to be elucidated, but selective tubular transport protein-mediated mechanisms likely play a role. In the present study, we investigate the human heteromeric transporter b0,+AT-rBAT (encoded by the SLC7A9 and SLC3A1 genes) as a potential candidate because it is localized in the luminal membrane of human proximal tubule cells and capable of mediating the cellular uptake of amino acids, including L-arginine. Double-transfected Madin-Darby canine kidney (MDCK) cells stably expressing human b0,+AT-rBAT exhibited significant uptake of L-arginine and L-homoarginine, with apparent Km values of 512.6 and 197.0 μM, respectively. On the contrary, ADMA uptake was not saturated up to 4000 μM, with a transport rate > 5 nmol × mg protein−1 × min−1. With an IC50 value of 115.8 μM, L-arginine inhibited L-homoarginine uptake. Conversely, L-arginine only exhibited a partial inhibitory effect on ADMA uptake. Taken together, our data indicate that b0,+AT-rBAT may contribute to the differential renal handling of L-arginine, L-homoarginine, and ADMA.