Resistance-Associated Proteins

Bakos E, Homolya L (2007) Portrait of multifaceted transporter, the multidrag resistance-associated protein 1 (MRP1/ABCC1). Pflugers Arch 453 621 641... 

A general mechanism of resistance is reducing the affinity of the antiretroviral compound for its mutant target protein. Resistance mutations associated with reduced affinity are observed during treatment failure with a fusion inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTl), integrase inhibitor, and protease inhibitors as reviewed in Chaps. 3,4, 6, and 7 (Hazuda et al. 2007 Hsiou et al. 2001 King et al. 2002 Mink et al. 2005). 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Sasaki M, Suzuki H, Aoki J, Ito K, Meier PJ and Sugiyama Y. Prediction of in vivo biliary clearance from the in vitro transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II monolayer expressing both rat organic anion transporting polypeptide 4 and multidrug resistance associated protein 2. Mol Pharmacol 2004 66 450-9. 

Aukunuru, JV, Sunkara, G, Bandi, N, Thoreson, WB, and Kompella, UB, 2001. Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor. Pharm Res 18, 565-572. 

Evers, R., G. J. Zaman, L. van Deemter, H. Jansen, J. Calafat, L. C. Oomen, R. P. Oude Elferink, P. Borst et al. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells,... 

Y., Function and expression of multidrug resistance-associated protein family in human colon adenocarcinoma cells (Caco-2),... 

Organic anion transporters can be divided into three major families organic anion transporters (OATs), organic anion transporting polypeptides (OATPs), and multidrug resistance associated proteins (MRPs) [201]. 

Borst, P., et al. A family of drug transporters the multidrug resistance-associated proteins. J. Natl. Cancer Inst. 2000, 92, 1295-1302. 

Williams, G. C., et al. Direct Evidence that Saquinavir Is Transported by Multidrag Resistance-Associated Protein (MRP1) and Canalicular Multispecific Organic Anion Transporter (MRP2). Antimicrob. Agents Chemother. 2002, 46, 3456-3462. 

Hirohashi, T., H. Suzuki, and Y. Sugiyama. Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3)./. Biol. Chem. 1999, 274, 15181-15185. 

Biliary Excretion Mediated by Multidrug Resistance-Associated Protein 2 (MRP2)... 

Zaman, G. J., Barker, C. T., Otter, M., Scheffer, G. L., Scheper, R. J., Borst, P., Oude Elferink, R. P., Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene, Science 1996, 271, 1126-1128. 

Suzuki, H., Sugiyama, Y., Single nucleotide polymorphisms in Multidrug Resistance Associated Protein... 

MRP1 Multidrug resistance-associated protein 1 (also designated ABCC1). 

MRP2 Multidrug resistance-associated protein 2 (also designated ABCC2). 

Seelig, A., Blatter, X. L., Wohnsiand, F., Substrate recognition by P-glycoprotein and the multidrug resistance-associated protein MRP1 a comparison, Int. J. Clin. Pharmacol. Ther. 2000, 38, 111-121. 

Rao W, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidmg resistance-associated protein contribute to the blood-cerebrospinalfluid drug-permeability barrier. Proc Natl Acad Sci USA 1999 96(7) 3900-3905. 

Regina A, Roman A, Piciotti M, El Hafny B, Center MS, Bergmann R et al. Mrpl multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J Neurochem 1998 71(2)705-715. 

Peng KC, Cluzeaud F, Bens M, van Huyen JP, Wioland MA, Lacave R et al. Tissue and cell distribution of the multidmg resistance-associated protein (MRP) in mouse intestine and kidney. J Histo-chem Cytochem 1999 47(6)757-768. 

Wijnholds J, Evers R, van Leusden MR, Mol CA, Zaman GJ, Mayer U et al. Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nature Med 1997 ... 

Kiuchi Y, Suzuki H, Hirohashi T, Tyson CA, Sugiyama Y. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett 1998 433(1—2) 149— 152. 

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