Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b<SUP>0,+</SUP>AT-rBAT (SLC7A9-SLC3A1)

Banjarnahor, Sofna and Scherpinski, Lorenz A. and Keller, Max and Koenig, Joerg and Maas, Renke (2025) Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b<SUP>0,+</SUP>AT-rBAT (SLC7A9-SLC3A1). NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 398 (4). pp. 4419-4434. ISSN 0028-1298, 1432-1912

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Abstract

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 b(0,+)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 b(0,+)AT-rBAT exhibited significant uptake of L-arginine and L-homoarginine, with apparent K-m values of 512.6 and 197.0 mu M, respectively. On the contrary, ADMA uptake was not saturated up to 4000 mu M, with a transport rate > 5 nmol x mg protein(-1) x min(-1). With an IC50 value of 115.8 mu M, L-arginine inhibited L-homoarginine uptake. Conversely, L-arginine only exhibited a partial inhibitory effect on ADMA uptake. Taken together, our data indicate that b(0,+)AT-rBAT may contribute to the differential renal handling of L-arginine, L-homoarginine, and ADMA.

Item Type: Article
Uncontrolled Keywords: RENAL CLEARANCE; HOMOARGININE; CYSTINURIA; DIMETHYLARGININE; KIDNEY; IDENTIFICATION; DYSFUNCTION; METABOLISM; EXPRESSION; MORTALITY; b(0,+)AT-rBAT; L-arginine; L-homoarginine; ADMA; Proximal tubule; Transport
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 31 Mar 2026 06:28
Last Modified: 31 Mar 2026 06:28
URI: https://pred.uni-regensburg.de/id/eprint/65094

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