title: 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 [(14)C]uric acid. Uric acid transport was saturable with K(m) of 1168+/-335 muM (mean and S.E.M.) and V(max) of 2.57+/-0.350 nmol/min/mg protein. The [(14)C]uric acid uptake was sensitive to Cl(-) and was enhanced at acidic pH. In cis-inhibition assay, [(14)C]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.
authors.affiliation: Kanazawa University, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Pharmacy, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mamada
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shirasaka
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
mesh_terms: D001692:Biological Transport; D002247:Carbon Isotopes; D002264:Carboxylic Acids / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D033461:Hyperuricemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D002264:Carboxylic Acids; D029362:Organic Anion Transporters, Sodium-Independent; D014527:Uric Acid