ABCC2/Abcc2: a multispecific transporter with dominant excretory functions

被引:112
|
作者
Jemnitz, Katalin [2 ]
Heredi-Szabo, Krisztina [1 ]
Janossy, Judit [1 ]
Ioja, Eniko [1 ]
Vereczkey, Laszlo [2 ]
Krajcsi, Peter [1 ]
机构
[1] SOLVO Biotechnol, H-2040 Budapest, Hungary
[2] HAS, Inst Biomol Chem, Chem Res Ctr, Budapest, Hungary
关键词
ABCC2; MRP2; ABC transporter; Dubin-Johnson syndrome; conjugate hyperbilirubinemia; pharmacokinetics; ADME; toxicity; MULTIDRUG-RESISTANCE PROTEIN-2; ORGANIC ANION-TRANSPORTER; CONJUGATE EXPORT PUMP; DUBIN-JOHNSON-SYNDROME; MRP2-DEFICIENT TR-RATS; BLOOD-BRAIN-BARRIER; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ISOLATED HEPATOCYTE COUPLETS; ATP-DEPENDENT TRANSPORT; KIDNEY PROXIMAL TUBULES;
D O I
10.3109/03602530903491741
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ABCC2/Abcc2 (MRP2/Mrp2) is expressed at major physiological barriers, such as the canalicular membrane of liver cells, kidney proximal tubule epithelial cells, enterocytes of the small and large intestine, and syncytiotrophoblast of the placenta. ABCC2/Abcc2 always localizes in the apical membranes. Although ABCC2/Abcc2 transports a variety of amphiphilic anions that belong to different classes of molecules, such as endogenous compounds (e. g., bilirubin-glucuronides), drugs, toxic chemicals, nutraceuticals, and their conjugates, it displays a preference for phase II conjugates. Phenotypically, the most obvious consequence of mutations in ABCC2 that lead to Dubin-Johnson syndrome is conjugate hyperbilirubinemia. ABCC2/Abcc2 harbors multiple binding sites and displays complex transport kinetics.
引用
收藏
页码:402 / 436
页数:35
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