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

Banjarnahor S, Scherpinski L, Keller M, König J, Maas R (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Naunyn-Schmiedeberg's Archives of Pharmacology Springer

Book Volume: 398

Pages Range: 4419-4434

DOI: 10.1007/s00210-024-03510-z

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 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 b^0,+AT-rBAT may contribute to the differential renal handling of L-arginine, L-homoarginine, and ADMA.

Authors with CRIS profile

Sofna Banjarnahor Professur für Arzneimitteltherapiesicherheit und Klinische Pharmakologie Lorenz Scherpinski Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Jörg König Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Renke Maas Professur für Arzneimitteltherapiesicherheit und Klinische Pharmakologie

Involved external institutions

Universität Regensburg

Germany (DE)

How to cite

APA:

Banjarnahor, S., Scherpinski, L., Keller, M., König, J., & Maas, R. (2024). Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b0,+AT-rBAT (SLC7A9-SLC3A1). Naunyn-Schmiedeberg's Archives of Pharmacology, 398, 4419-4434. https://doi.org/10.1007/s00210-024-03510-z

MLA:

Banjarnahor, Sofna, et al. "Differential uptake of arginine derivatives by the human heteromeric amino acid transporter b0,+AT-rBAT (SLC7A9-SLC3A1)." Naunyn-Schmiedeberg's Archives of Pharmacology 398 (2024): 4419-4434.

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