Document Detail


Renal secretion of uric acid by organic anion transporter 2 (OAT2/SLC22A7) in human.
MedLine Citation:
PMID:  20190416     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Masanobu Sato; Hideaki Mamada; Naohiko Anzai; Yoshiyuki Shirasaka; Takeo Nakanishi; Ikumi Tamai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological & pharmaceutical bulletin     Volume:  33     ISSN:  1347-5215     ISO Abbreviation:  Biol. Pharm. Bull.     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-01     Completed Date:  2010-09-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9311984     Medline TA:  Biol Pharm Bull     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  498-503     Citation Subset:  IM    
Affiliation:
Kanazawa University, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Pharmacy, Japan.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Carbon Isotopes
Carboxylic Acids / pharmacology
Cell Line
Humans
Hydrogen-Ion Concentration
Hyperuricemia / metabolism*
Kidney / metabolism*
Organic Anion Transporters, Sodium-Independent / metabolism*
Uric Acid / blood,  metabolism*
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/Carboxylic Acids; 0/Organic Anion Transporters, Sodium-Independent; 69-93-2/Uric Acid

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