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Multiple organic anion transporters contribute to net renal excretion of uric acid
- Publication Year :
- 2008
-
Abstract
- Excretion of uric acid, a compound of considerable medical importance, is largely determined by the balance between renal secretion and reabsorption. The latter process has been suggested to be principally mediated by urate transporter 1 (URAT1; slc22a12), but the role of various putative urate transporters has been much debated. We have characterized urate handling in mice null for RST, the murine ortholog of URAT1, as well as in those null for the related organic anion transporters Oat1 and Oat3. Expression of mRNA of other putative urate transporters (UAT, MRP2, MRP4, Oatv1) was unaffected in the knockouts, as were general indexes of renal function (glomerular filtration rate, fractional excretion of fluid and electrolytes). While mass spectrometric analyses of urine and plasma revealed significantly diminished renal reabsorption of urate in RST-null mice, the bulk of reabsorption, surprisingly, was preserved. Oat1- and Oat3-null mice manifested decreased secretion rather than reabsorption, indicating that these related transporters transport urate in the “opposite” direction to RST. Moreover, metabolomic analyses revealed significant alteration in the concentration of several molecules in the plasma and urine of RST knockouts, some of which may represent additional substrates of RST. The results suggest that RST, Oat1, and Oat3 each contribute to urate handling, but, at least in mice, the bulk of reabsorption is mediated by a transporter(s) that remains to be identified. We discuss the data in the context of recent human genetic studies that suggest that the magnitude of the contribution of URAT1 to urate reabsorption might vary with ethnic background.
- Subjects :
- medicine.medical_specialty
Organic anion transporter 1
Physiology
Organic Anion Transporters
Kidney
Article
Excretion
chemistry.chemical_compound
Mice
Internal medicine
Genetics
medicine
Animals
RNA, Messenger
Mice, Knockout
biology
Reabsorption
Renal Reabsorption
Membrane Proteins
Biological Transport
beta-Galactosidase
Uric Acid
medicine.anatomical_structure
Endocrinology
Phenotype
chemistry
Biochemistry
Gene Expression Regulation
Renal physiology
Gene Targeting
biology.protein
Organic anion transport
Uric acid
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1201fb41e4ae95a90669f751c2773e88