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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.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Habu Y,Yano I,Okuda M,Fukatsu A,Inui K

doi

10.1016/j.bcp.2004.12.004

subject

Has Abstract

pub_date

2005-03-15 00:00:00

pages

993-9

issue

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(04)00820-2

journal_volume

pub_type

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