Multidrug resistant associated protein

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. 

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. 

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. 

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. 

Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 2000 275(4)2905-2910. 

Hirohashi T, Suzuki H, Ito K, Ogawa K, Kume K, Shimizu T et al. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in eisai hyperbilirubinemic rats. Mol Pharmacol 1998 53(6) 1068-1075. 

Soroka CJ, Lee JM, Azzaroli F, Boyer JL. Cellular localization and up-regula-tion of multidrug resistance-associated protein 3 in hepatocytes and cholangio-cytes during obstructive cholestasis in rat liver. Hepatology 2001 33(4) 783 791. 

The presence at the BBB of members of the multidrug resistance-associated protein (MRPs) family, whose members preferentially transport anionic compounds, is still controversial. The seven members of the MRP family belong, like P-gp, to the ATP-binding cassette (ABC) protein superfamily. Mrpl has been found at the BBB in isolated rat brain capillaries, primary cultures of brain capillary endothelial cells and in immortalized capillary endothelial cells, but not in human brain capillaries [59]. Another member, MRP2 has been found at the luminal membrane of the brain endothelial cells [60]. However, further studies are required to show that there are MRP transporters at the BBB (Figure 15.5). As for P-gp, a functional Mrpl was found in primary cultured rat astrocytes [56] and it has been shown to take part in the release of glutathione disulfide from brain astrocytes under oxidative stress [61]. 

J. A family of dmg transporters The multidrug resistance-associated proteins. 

Kast, H.R., Goodwin, B., Tarr, P.T., Jones, S.A., Anisfeld, A.M., Stoltz, C.M., Tontonoz, P., Kliewer, S., Willson, T.M. and Edwards, P.A. (2002) Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. Journal of Biological Chemistry, 277, 2908-2915. 

Zhang, Y., Schuetz, J.D., Elmquist, W.F. and Miller, D.W. (2004) Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells. Journal of Pharmacology and Experimental Therapeutics, 311, 449-455. 

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