Mouse GLUT9: evidences for a urate uniporter

Departments of 1 Pharmacology and Toxicology and 2 Physiology 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. [ 14 C]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 [ 14 C]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 Address for reprint requests and other correspondence: O. Bonny, Dept. of Pharmacology and Toxicology, Univ. of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland (e-mail: Olivier.Bonny{at}unil.ch )