Multidrug resistance protein (MRP) 2 (MRP2; ABCC2), an organic anion transporter apically expressed in liver, kidney, and intestine, plays an important protective role through facilitating the efflux of potentially toxic compounds. We hypothesized that upon a toxic insult, MRP2 is up-regulated in mammalian kidney, thereby protecting the tissue from damage. We studied the effects of the nephroto...

The multidrug transporters breast cancer resistance protein (BCRP), multidrug-resistance protein 1 (MDR1), and multidrug-resistance-associated protein (MRP) 2 and 3 eliminate toxic compounds from tissues and the body and affect the pharmacokinetics of many drugs and other potentially toxic compounds. The food-derived carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is transport...

Despite the recent introduction of the new anticancer agents gemcitabine (GEM) and TS-1, as well as combination regimens such as GEM plus cisplatin (CDDP), pancreatic cancer treatment remains relatively ineffective. Both intrinsic and acquired resistance to chemotherapy are major roadblocks to the successful treatment of pancreatic cancer patients. The aims of this study were to examine the exp...

The platinum-based anticancer drug oxaliplatin is important clinically in cancer treatment. However, the role of multidrug resistance-associated protein 2 (MRP2) in controlling oxaliplatin membrane transport, in vivo handling, toxicity and therapeutic responses is unclear. In the current study, preparations of MRP2-expressing and control membrane vesicles, containing inside-out orientated vesic...

The effect of the cholestatic estrogens ethynylestradiol (EE) and estradiol 17beta-D-glucuronide (E2-17G) on expression and activity of intestinal multidrug resistant-associated protein 2 (Mrp2, Abcc2) was studied in rats. Expression and localization of Mrp2 were evaluated by Western blotting, real-time polymerase chain reaction, and confocal immunofluorescence microscopy. Mrp2 transport activi...

A novel ATP-dependent export pump for amphiphilic anionic conjugates, which has been cloned recently from liver, was identified in rat kidney and localized to the apical membrane domain of proximal tubule epithelia. This 190-kD membrane glycoprotein (Mrp2) has been described previously as the hepatocyte canalicular isoform of the multidrug resistance protein and as the canalicular multispecific...

We recently demonstrated in isolated killifish renal proximal tubules that two classes of nephrotoxicants, aminoglycoside antibiotics and radiocontrast agents, rapidly decrease transport mediated by multidrug resistance protein 2 (Mrp2) by causing endothelin (ET) release and signaling through an ET(B) receptor and protein kinase C (PKC). In the present study, we used killifish proximal tubules,...

Human organic anion transporting polypeptide 2 (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2) play important roles in the vectorial transport of organic anions across hepatocytes. In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and apical membranes, respect...

The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial...

Oxidative stress is known to be a common feature of cholestatic syndrome. We have described the internalization of multidrug resistance-associated protein 2 (Mrp2), a biliary transporter involved in bile salt-independent bile flow, under acute oxidative stress, and a series of signaling pathways finally leading to the activation of novel protein kinase C were involved in this mechanism; however...