title: Identification and functional characterization of uric acid transporter Urat1 (Slc22a12) in rats.
abstract: Uric acid transporter URAT1 contributes significantly to reabsorption of uric acid in humans to maintain a constant serum uric acid (SUA) level. Since alteration of SUA level is associated with various diseases, it is important to clarify the mechanism of change in SUA. However, although expression of mRNA of an ortholog of URAT1 (rUrat1) in rats has been reported, functional analysis and localization have not been done. Therefore, rat rUrat1 was functionally analyzed using gene expression systems and isolated brush-border membrane vesicles (BBMVs) prepared from rat kidney, and its localization in kidney was examined immunohistochemically. Uric acid transport by rUrat1 was chloride (Cl-) susceptible with a Km of 1773μM. It was inhibited by benzbromarone and trans-stimulated by lactate and pyrazinecarboxylic acid (PZA). Cl- gradient-susceptible uric acid transport by BBMVs showed similar characteristics to those of uric acid transport by rUrat1. Moreover, rUrat1 was localized at the apical membrane in proximal tubular epithelial cells in rat kidney. Accordingly, rUrat1 is considered to be involved in uric acid reabsorption in rats in the same manner as URAT1 in humans. Therefore, rUrat1 may be a useful model to study issues related to the role of human URAT1.
authors.affiliation: Faculty of Pharmacy, Department of Histology and Embryology, Graduate School of Medical Science, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sato
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mamada
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: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001553:Benzbromarone / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011718:Pyrazinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014527:Uric Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D014982:Xenopus laevis
chemical_list: D027321:Anion Transport Proteins; D007773:Lactates; C554079:Slc22a12 protein, rat; D014527:Uric Acid; D011718:Pyrazinamide; C005296:pyrazinoic acid; D001553:Benzbromarone