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Increased hepatic and renal expressions of multidrug resistance-associated protein 3 in Eisai hyperbilirubinuria rats

Background and Aim:  Eisai hyperbilirubinuria rats (EHBR) are animal models of Dubin–Johnson syndrome, which suffer from jaundice due to impaired biliary excretion of bilirubin glucuronides. In EHBR, deficiency of multidrug resistance‐associated protein 2 (mrp2) causes defective biliary excretion of...

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Published in:Journal of gastroenterology and hepatology 2004-02, Vol.19 (2), p.146-153
Main Authors: KURODA, MAKOTO, KOBAYASHI, YOSHINAO, TANAKA, YUJI, ITANI, TOSHIO, MIFUJI, RUMI, ARAKI, JUN, KAITO, MASAHIKO, ADACHI, YUKIHIKO
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Language:English
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Summary:Background and Aim:  Eisai hyperbilirubinuria rats (EHBR) are animal models of Dubin–Johnson syndrome, which suffer from jaundice due to impaired biliary excretion of bilirubin glucuronides. In EHBR, deficiency of multidrug resistance‐associated protein 2 (mrp2) causes defective biliary excretion of numerous organic anions. However, little is known about the expression of other organic anion transporters in this mrp2‐deficient model. The aim of the present study was to investigate adaptive expressions of mrp1, mrp3, mrp6, organic anion transporting polypeptide 1 (oatp1) and oatp2 in liver and kidney of EHBR. Methods:  For the present study, EHBR (n = 5) were used. Hepatic and renal mRNA expression of the aforementioned transporters was determined by constructed semiquantitative reverse transcription polymerase chain reaction assay. Their protein expression was determined by western blotting. Localization of hepatic and renal mrp3 was confirmed by immunohistochemistry. Sprague–Dawley (SD) rats (n = 5) were used as normal controls. Results:  Deficiency of mrp2 protein was confirmed in EHBR. Hepatic and renal expression of mrp3 mRNA was 53.6% (P 
ISSN:0815-9319
1440-1746
DOI:10.1111/j.1440-1746.2004.03275.x