CONTEXT Chemoresistance is due to the expression of multidrug-resistance proteins (MRPs). Cyclooxygenase 2 (COX2), a key enzyme in prostaglandins synthesis, upregulates MRP1. MRP1 is overexpressed in medullary thyroid carcinomas (MTCs), but it is not involved in resistance to doxorubicin and cisplatin, which are commonly used in MTC treatment. MRP2 is specifically involved in resistance to both...

Mottino, Aldo D., Fernando A. Crocenzi, Enrique J. Sánchez Pozzi, Luis M. Veggi, Marcelo G. Roma, and Mary Vore. Role of microtubules in estradiol-17 -D-glucuronide-induced alteration of canalicular Mrp2 localization and activity. Am J Physiol Gastrointest Liver Physiol 288: G327–G336, 2005. First published September 16, 2004; doi:10.1152/ajpgi.00227.2004.—Estradiol-17 -D-glucuronide (E2-17G) i...

p-Aminohippurate (PAH) is the classical substrate used in the characterization of organic anion transport in renal proximal tubular cells. Although basolateral transporters for PAH uptake from blood into the cell have been well characterized, there is still little knowledge on the apical urinary efflux transporters. The multidrug resistance protein 2 (MRP2/ABCC2) is localized to the apical memb...

Regulation of multidrug resistance-associated protein (MRP2) expression in response to dexamethasone (DEX) was analyzed using mainly primary rat hepatocytes. Enhanced levels of MRP2 mRNAs associated with increased amounts of a 190 kDa MRP2 were found in cultured DEX-treated hepatocytes; similarly, administration of DEX to rats (100 mg/kg, i.p.) led to a marked increase of hepatic amounts of MRP...

Multidrug resistance-associated protein 2 (MRP2) plays an important role in bile acid metabolism by transporting toxic organic anion conjugates, including conjugated bilirubin, glutathione, sulfate, and multifarious drugs. MRP2 expression is reduced in cholestatic patients and rodents. However, the molecular mechanism of MRP2 down-regulation remains elusive. In this report, we treated human hep...

PKI166, a specific inhibitor of the tyrosine kinase activity of two epidermal growth factor receptors, was under development for the treatment of cancer. In preclinical studies PKI166 was mainly cleared by metabolism, and its metabolites were eliminated by biliary excretion, emphasizing the role of liver transport processes for its disposition. Here the transport properties of [14C]PKI166 and i...

The multidrug resistance protein 2 (MRP2/ABCC2) mediates the biliary excretion of glucuronide and glutathione conjugates of endogenous and exogenous compounds. We examined the activation of human MRP2-mediated ATP-dependent transport by the choleretic bile salt ursodeoxycholic acid (UDC) and its taurine and glycine amidates in Sf9 cell membranes expressing MRP2 using beta-estradiol 17-(beta-D-g...

We investigated whether the species difference in the biliary excretion activity of some Mrp2 substrates was attributable to the intrinsic transport potential or the expression level of Mrp2, especially in rat and dog. Dog Mrp2 cDNA was isolated from beagle dog liver, and a vesicle transport study was performed using recombinant rat and dog Mrp2 expressed in insect Sf9 cells. The ATP-dependent ...

the drug pump protein mrp2 is a membrane drug efflux transporter widely distributed in normal and tumor tissues. its role is thought to be crucial for the disposition of many drugs and their substrates in different tissues. in this study, we aimed to examine the effects of systematic inflammation induced by lipopolysaccharide (lps) on the expression and function of this transporter in rats. jug...

Multidrug resistance protein 2 (ABCC2/MRP2) is an ATP-binding cassette transporter involved in the absorption, distribution, and excretion of drugs and xenobiotics. Identifying compounds that are ABCC2/MRP2 substrates and/or inhibitors and understanding their structure-activity relationships (SARs) are important considerations in the selection and optimization of drug candidates. In the present...