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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/F612    most recent 00139.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bibert, S. Articles by Bonny, O. PubMed PubMed Citation Articles by Bibert, S. Articles by Bonny, O.

Mouse GLUT9: evidences for a urate uniporter

Stéphanie Bibert,¹ Solange Kharoubi Hess,¹ Dmitri Firsov,¹ Bernard Thorens,² Käthi Geering,¹ Jean-Daniel Horisberger,^1, and Olivier Bonny¹

Departments of ¹Pharmacology and Toxicology and ²Physiology and Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Submitted 8 March 2009 ; accepted in final form 3 July 2009

GLUT9 (SLC2A9) is a newly described urate transporter whose function, characteristics, and localization have just started to be elucidated. Some transport properties of human GLUT9 have been studied in the Xenopus laevis oocyte expression system, but the type of transport (uniport, coupled transport system, stoichiometry ... .) is still largely unknown. We used the same experimental system to characterize in more detail the transport properties of mouse GLUT9, its sensitivity to several uricosuric drugs, and the specificities of two splice variants, mGLUT9a and mGLUT9b. [¹⁴C]urate uptake measurements show that both splice variants are high-capacity urate transporters and have a K_m of 650 µM. The well-known uricosuric agents benzbromarone (500 µM) and losartan (1 mM) inhibit GLUT9-mediated urate uptake by 90 and 50%, respectively. Surprisingly, phloretin, a glucose-transporter blocker, inhibits [¹⁴C]urate uptake by 50% at 1 mM. Electrophysiological measurements suggest that urate transport by mouse GLUT9 is electrogenic and voltage dependent, but independent of the Na⁺ and Cl^– transmembrane gradients. Taken together, our results suggest that GLUT9 works as a urate (anion) uniporter. Finally, we show by RT-PCR performed on RNA from mouse kidney microdissected tubules that GLUT9a is expressed at low levels in proximal tubules, while GLUT9b is specifically expressed in distal convoluted and connecting tubules. Expression of mouse GLUT9 in the kidney differs from that of human GLUT9, which could account for species differences in urate handling.

uric acid; SLC2A9; splice variants