MRP multidrug resistance-associated

MRPs Multidrug resistant-associated protein isoforms... 

L-Amph amphotericin B liposome MRP multidrug resistance-associated protein... 

ABC, ATP-binding cassette AML, acute mylogenous leukemia NSCLC, non-small-cell lung cancer NSAIDs, non-steroidal anti-inflammatory drugs BCRP, breast cancer resistance protein MDRl, multidrug resistance 1 MRP, multidrug resistance-associated proteins P-gp, P-glycoprotein. 

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. 

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. 

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]. 

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]. 

Zaman, G.J., Flens, M.J., van Leusden, M.R., de Haas, M., Mulder, H.S., Lankelma, J., Pinedo, H.M., Scheper, R. J., Baas, F. and Broxterman, H.J., (1994) The human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump. Proceedings of the National Academy of Sciences of the United States of America, 91, 8822-8826. 

Zhang, Y, Han, H, Elmquist, WF, MMiiler, DW (2000) Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells. Brain Res 876 148-153. 

Zhang Y, Schuetz JD, Elmquist WF, Miller DW (2004) Plasma membrane localization of multidrug resistance-associated protein (MRP) homologues in brain capillary endothelial cells. J Pharmacol Exp Ther 311 449-55... 

Johnson BM, Zhang P, Schuetz J, Brouwer KL (2006) Characterization of transport protein expression in multidrug resistance-associated protein (MRP)2-deficant rats. Drug Metab Dispos 34 556-62... 

Active efflux transporters also exist in the placenta, analogous to the gut and blood-brain barrier. These are Pgp, multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP). These transport proteins are located in many tissues but also appear to be expressed in the placenta. Though the substrate specificities of these proteins have not been completely described, they appear to function as efflux transporters, moving endogenous and exogenous chemicals from the placental cells back to the systemic circulation. In this way, they serve as a mechanism to protect the fetus from exposure to unintended chemicals. 

Efflux transporters, such as multidrug resistant protein, known as P-glycoprotein (Pgp), and related multidrug-resistant associated protein isoforms (MRPs), have been shown to be important for structurally diverse lipophilic compounds. Pgp and several MRPs, which were first identified in... 

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