Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after hyperuricemia in the rat kidney.

Abstract

We previously reported that in hyperuricemic rats, renal impairment occurred and organic ion transport activity decreased, accompanied with a specific decrease in the expression of rat organic anion transporters, rOAT1 and rOAT3, and organic cation transporter, rOCT2. In the present study, we investigated the reversibility of the organic ion transport activity and expression of organic ion transporters (slc22a) during recovery from hyperuricemia. Hyperuricemia was induced by the administration of a chow containing uric acid and oxonic acid, an inhibitor of uric acid metabolism. Four days after discontinuance of the chow, the plasma uric acid concentration returned to the normal level, and renal functions such as creatinine clearance and BUN levels were restored, although the recovery of tubulointerstitial injury was varied in sites of the kidney. Basolateral uptake of p-aminohippurate (PAH) and tetraethylammonium (TEA), and both protein and mRNA levels of rOAT1, rOAT3 and rOCT2 in the kidney gradually improved during 14 days of recovery from hyperuricemia. Basolateral PAH transport showed a higher correlation with the protein level of rOAT1 (r(2)=0.80) than rOAT3 (r(2)=0.34), whereas basolateral TEA transport showed a strong correlation with rOCT2 protein (r(2)=0.91). The plasma testosterone concentration, which is a dominant factor in the regulation of rOCT2, was gradually restored during the recovery from hyperuricemia, but the correlation between the plasma testosterone level and rOCT2 protein expression in the kidney was not significant. These results suggest that the regulation of organic ion transporters, rOAT1, rOAT3 and rOCT2, by hyperuricemia is reversible, and the organic ion transport activity restores according to the expression levels of these transporters.

• Authors: Yasushi Habu, Ikuko Yano, Masahiro Okuda, Atsushi Fukatsu, Ken-ichi Inui
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 69 Issue 6 Pg. 993-9 (Mar 15 2005) ISSN: 0006-2952 [Print] England
• PMID: 15748710 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Organic Anion Transport Protein 1
• Organic Anion Transporters, Sodium-Independent
• Organic Cation Transport Proteins
• Organic Cation Transporter 2
• Slc22a2 protein, rat
• Slc22a6 protein, rat
• organic anion transport protein 3

Topics

• Animals
• Gene Expression Regulation (physiology)
• Hyperuricemia (genetics, metabolism)
• Kidney (metabolism)
• Male
• Organic Anion Transport Protein 1 (biosynthesis, genetics, metabolism)
• Organic Anion Transporters, Sodium-Independent (biosynthesis, genetics, metabolism)
• Organic Cation Transport Proteins (biosynthesis, genetics, metabolism)
• Organic Cation Transporter 2
• Rats
• Rats, Wistar