Urate transport function of rat sodium-dependent nucleobase transporter 1

Physiological Reports
Tomoya YasujimaHiroaki Yuasa

Abstract

Sodium-dependent nucleobase transporter 1 (SNBT1) is a nucleobase-specific transporter identified in our recent study. In an attempt to search for its potential substrates other than nucleobases in this study, we could successfully find urate, a metabolic derivative of purine nucleobases, as a novel substrate, as indicated by its specific Na+ -dependent and saturable transport, with a Michaelis constant of 433 μmol/L, by rat SNBT1 (rSNBT1) stably expressed in Madin-Darby canine kidney II cells. However, urate uptake was observed only barely in the everted tissue sacs of the rat small intestine, in which rSNBT1 operates for nucleobase uptake. These findings suggested that urate undergoes a futile cycle, in which urate transported into epithelial cells is immediately effluxed back by urate efflux transporters, in the small intestine. In subsequent attempts to examine that possibility, such a futile urate cycle was demonstrated in the human embryonic kidney 293 cell line as a model cell system, where urate uptake induced by transiently introduced rSNBT1 was extensively reduced by the co-introduction of rat breast cancer resistance protein (rBCRP), a urate efflux transporter present in the small intestine. However, urate uptake was...Continue Reading

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Citations

Mar 8, 2020·Medicinal Research Reviews·Gustavo D Campagnaro, Harry P de Koning
Sep 4, 2020·Biological & Pharmaceutical Bulletin·Hiroaki YuasaKatsuhisa Inoue
Apr 7, 2020·Drug Metabolism and Pharmacokinetics·Masaki TakahashiKatsuhisa Inoue
Feb 20, 2021·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Chenjie YangQiaoling Zhao

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Methods Mentioned

BETA
PCR
transfection

Software Mentioned

WinNonlin

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