Mouse GLUT9: evidences for a urate uniporter.

Détails

ID Serval
serval:BIB_AE08062CF747
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mouse GLUT9: evidences for a urate uniporter.
Périodique
American Journal of Physiology. Renal Physiology
Auteur(s)
Bibert S., Hess S.K., Firsov D., Thorens B., Geering K., Horisberger J.D., Bonny O.
ISSN
1522-1466 (Electronic)
ISSN-L
1522-1466
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
297
Numéro
3
Pages
F612-F619
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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 approximately 650 microM. The well-known uricosuric agents benzbromarone (500 microM) 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 approximately 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.
Mots-clé
Animals, Benzbromarone/pharmacology, Biological Transport, Chlorides/metabolism, Glucose/metabolism, Glucose Transport Proteins, Facilitative/antagonists & inhibitors, Glucose Transport Proteins, Facilitative/genetics, Glucose Transporter Type 2/metabolism, Kinetics, Losartan/pharmacology, Male, Membrane Potentials, Mice, Mice, Inbred C57BL, Nephrons/metabolism, Oocytes, Organic Anion Transporters/antagonists & inhibitors, Organic Anion Transporters/genetics, Phloretin/pharmacology, Protein Isoforms, RNA, Messenger/analysis, Sodium/metabolism, Species Specificity, Uric Acid/metabolism, Uricosuric Agents/pharmacology, Xenopus laevis
Pubmed
Web of science
Création de la notice
14/07/2009 9:46
Dernière modification de la notice
20/08/2019 15:17
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