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

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-exp...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2010/03/01, Vol.33(3), pp.498-503
Main Authors: Sato, Masanobu, Mamada, Hideaki, Anzai, Naohiko, Shirasaka, Yoshiyuki, Nakanishi, Takeo, Tamai, Ikumi
Format: Article
Language:English
Subjects:
antiuricosuric
Biological Transport
Carbon Isotopes
Carboxylic Acids - pharmacology
Cell Line
Humans
Hydrogen-Ion Concentration
Hyperuricemia - metabolism
Kidney - metabolism
organic anion transporter 2
Organic Anion Transporters, Sodium-Independent - metabolism
serum uric acid level
transporter
uric acid
Uric Acid - blood
Uric Acid - metabolism
uricosuric
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Summary: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 [14C]uric acid. Uric acid transport was saturable with Km of 1168±335 μM (mean and S.E.M.) and Vmax of 2.57±0.350 nmol/min/mg protein. The [14C]uric acid uptake was sensitive to Cl− and was enhanced at acidic pH. In cis-inhibition assay, [14C]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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.33.498