ABCC2/Abcc2: a multispecific transporter with dominant excretory functions

• Published in: Drug metabolism reviews Vol. 42; no. 3; pp. 402 - 436
• Main Authors: Jemnitz, Katalin, Heredi-Szabo, Krisztina, Janossy, Judit, Ioja, Eniko, Vereczkey, Laszlo, Krajcsi, Peter
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.08.2010; Taylor & Francis
• Subjects: ABC transporter; ABCC2; ADME; Animals; Biological Transport, Active; Cloning, Molecular; conjugate hyperbilirubinemia; Drug Resistance, Multiple; Dubin-Johnson syndrome; Humans; Kinetics; Mice; Mice, Knockout; MRP2; Multidrug Resistance-Associated Proteins - biosynthesis; Multidrug Resistance-Associated Proteins - chemistry; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; pharmacokinetics; Protein Conformation; toxicity; Xenobiotics - metabolism
• ISSN: 0360-2532; 1097-9883
• DOI: 10.3109/03602530903491741

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.