Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human

Abstract

The physiological function of organic anion transporter OAT2 (SLC22A7) remains unclear, but since OAT2 transports purine derivatives, it may be involved in renal handling of uric acid, the final metabolite of purine derivatives. In the present study, we studied uric acid transport in stably OAT2-expressing HEK293 cells (HEK293/OAT2). OAT2 mediated uptake, but not efflux, of [ ]uric acid uptake was inhibited by several mono-or dicarboxylic acids, but it was not trans-stimulated by any of the compounds tested. The pattern of inhibition of OAT2-mediated uric acid transport by various drugs was different from that of OAT1-or OAT3-mediated transport. Furthermore, OAT2-mediated transport of uric acid was inhibited by an antiuricosuric drug, pyrazinecarboxylic acid. These results revealed distinct characteristics of uric acid transport via OAT2 compared with other uric acid transporters, suggesting that OAT2 plays a role in renal uric acid uptake from blood as a first step of tubular secretion. OAT2 may therefore be a potential target for regulating serum uric acid level.

The Molecular Physiology of Uric Acid Homeostasis

“…OAT2 is also less sensitive to benzbromarone and probenecid than are other urate transporters. Urate transport in OAT2-expressing HEK293 cells is cis-inhibited, but not transactivated, by both monocarboxylates and dicarboxylates, including PZA (126); this analysis leaves uncharacterized the endogenous anions that exchange with urate on OAT2 in vivo. However, a significant role in human urate homeostasis is indicated by a small but measurable effect on SUA of variation in the SLC22A7 gene, which encodes human OAT2 (16).…”

“…The OAT2 protein is expressed at the basolateral membrane of human proximal tubule cells (125). OAT2 has a more restricted substrate specificity than do OAT1 and OAT3 (126). OAT2 is also less sensitive to benzbromarone and probenecid than are other urate transporters.…”

Interaction of human organic anion transporter 2 (OAT2) and sodium taurocholate cotransporting polypeptide (NTCP) with antineoplastic drugs

“…It has been shown to be expressed predominantly in liver, and to a lesser extent in kidney, lung and various other tissues in humans [2,3]. Its substrates include many endogenous substances like cGMP, estrone 3-sulfate, dehydroepiandrosterone sulfate, prostaglandin E2, purine analogs, glutamate, orotic acid, uric acid, and exogenous substrates including tetracycline, antiviral compounds like acyclovir, ganciclovir, zidovudine, and paclitaxel among others [4][5][6][7][8].…”

Urate transporters in the genomic era

“…In a recent GWAS, an SNP in the OAT2 gene (SLC22A7) has been associated with serum urate levels but not with gout [6 && ]. Together with a recent functional study [27] showing that OAT2 can transport urate, OAT2 may be a good candidate for urate uptake transporter located in the basolateral side of the proximal tubule.…”