NDLI: Treatment of Hyperbilirubinemia in Eisai Hyperbilirubinemic Rat by Transfecting Human MRP2/ABCC2 Gene

Content Provider	Springer Nature Link
Author	Hirouchi, Masakazu Suzuki, Hiroshi Sugiyama, Yuichi
Copyright Year	2005
Abstract	Multidrug resistance-associated protein 2 (MRP2/ABCC2) is predominantly expressed in the liver canalicular membrane and plays an important role in the biliary excretion of organic anions including glucuronide and glutathione conjugates. The purpose of this study is to construct a new evaluation system for human MRP2 by expressing human MRP2 in Eisai hyperbilirubinemic rat (EHBR) liver, the rat Mrp2 function of which is hereditarily defective.In order to express human MRP2 in liver, we used the Tet-off adenovirus expression system. After 72 h infection, we evaluated the protein expression and localization in the liver and the transport activity of [$^{3}$H]E$_{2}$17ßG and [$^{3}$H]DNP-SG by preparing canalicular membrane vesicles (CMVs). We also evaluated the biliary excretion and plasma concentration of DBSP after bolus administration and the plasma concentration of endogenous direct and indirect bilirubin.The localization of human MRP2 in EHBR liver was found to be at the bile canalicular membrane. Clear ATP-dependent uptake of [$^{3}$H]E$_{2}$17ßG and [$^{3}$H]DNP-SG into CMVs was observed by using the CMVs prepared from the liver where human MRP2 was transfected. Furthermore, the blood to bile clearance of DBSP increased approximately 3-fold after expression of human MRP2. In addition, the plasma direct bilirubin level in EHBR was reduced by the expression of human MRP2.These results suggest that this evaluation system for human MRP2 may be useful for evaluating the function of human MRP2.
Starting Page	661
Ending Page	666
Page Count	6
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	22
Issue Number	4
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2005-04-07
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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