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Interaction of a novel urate efflux transporter URATv1 ( SLC2A9 ) with uricosuric agents.
Author(s) -
Anzai Naohiko,
Jin Chun Ji,
Jutabha Promsuk,
Babu Ellappan,
Srivastava Sunena,
Endou Hitoshi,
Sakurai Hiroyuki
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.797.10
Subject(s) - hyperuricemia , benzbromarone , uricosuric , chemistry , probenecid , organic anion transporter 1 , uric acid , reabsorption , endocrinology , cotransporter , transporter , medicine , efflux , hypouricemia , biochemistry , kidney , biology , organic chemistry , gene , sodium
Hyperuricemia is a significant factor in a variety of diseases, including gout and cardiovascular diseases. And renal excretion largely determines plasma urate concentration. Previously we identified a major urate reabsorptive transporter, URAT1 ( SLC22A12 ), on the apical side of the renal proximal tubular cells. Recently, we identified that URATv1 ( SLC2A9 ) functions as an efflux transporter of urate from the tubular cell. URATv1‐expressed Xenopus oocytes transported urate favoring negative to positive potential direction. Considering its basolateral localization, SLC2A9 is likely to mediate the second step of urate reabsorption. To further characterize the transport properties of URATv1, we performed the urate transport studies in the URATv1 expressed oocytes. URATv1‐mediated urate transport was not trans ‐stimulated by intracellularly‐injected glucose, fructose, monocarboxylates such as lactate, nicotinate or pyrazinoate (PZA) for urate. In addition, urate efflux via URATv1 was not enhanced by extracellular glucose or fructose. Urate transport via URATv1 was affected by uricosuric agents probenecid, benzbromarone, phenylbutazone and losartan, but not by monocarboxylates such as lactate, nicotinate, orotate, PZA, or β‐hydroxybutyrate. In summary, different substrate selectivity between URATv1 and URAT1 suggests that targeting URATv1 may lead to a novel therapy for hyperuricemia.