Multi drug transporter

Ozvegy-Laczka C, Elegedus T, Varady G et al. High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multi drug transporter. Mol Pharmacol 2004 65 1485-1495. 

Sharom FJ. The P-glycoprotein multi drug transporter interactions with membrane lipids, and their modulation of activity. Biochem Soc Trans 1997 25(3) 1088-1096. 

Fig. 6 Multi-drug transporters in the human liver hepatocytes. Abbreviations TJ Tight junction. (Reproduced from [4])...

Gottesman, M. M., Pastan, T. Biochemistry of multi-drug resistance mediated by the multi-drug transporter. Arum. Rev. Biochem. 1993,... 

M. Monod and J. Bille (1995). Mechanisms of resistance to azole antifungal agents in Candida albicans from AIDS patients involve specific multi-drug transporters. Antimicrob. Agents... 

The first cloned sequences of the multi-drug resistance transporter (P-glycoprotein, MDR1, ABCB1) were isolated from multi-resistant cell lines in which the gene was strongly amplified. By in-gel renaturation analysis these... 

Figure 2.1 Hepatocyte basolateral bile acid transporters. Protein-bound bile acids returning in portal blood are taken up by the hepatocyte via the sodium taurocholate co-transporting polypeptide (NTCP) and organic-anion-transporting polypeptide (OATP). In cholestasis bile acids may be returned to blood by the multi-drug-resistance-associated protein 3 (MRP3).

Figure 2.3 Absorption of bile acids by the cholangiocyte in the cholehepatic shunt. Bile acids are absorbed at the apical membrane of the cholangioc5de by the apical sodium-dependent bile-acid transporter (ASBT) that causes cholehepatic shunting of bile acids back to the hepatocyte. Absorbed bile adds are exported across the basolateral membrane by multi-drug-resistance-associated protein 3 (MRP3), a truncated form of ASBT or by the het-eromeric organic solute (OST) a and p forms. Bile adds cause choleresis that is rich in bicarbonate ions secreted by the chloride/bicarbonate ion exchanger.

The use of so-called reversal agents to block P-gp in order to decrease multi-drug resistance, will therefore also affect the elimination rate of those anti-cancer agents that are substrates for this transport system [19]. 

Nissler, L., Gebhardt, R., and Berger, S., Flavonoid binding to a multi-drug-resistance transporter protein an STD-NMR study. Anal Bioanal Chem., 379, 1045, 2004. 

Multi-drug resistance protein-2 (MRP-2) A protein in the bile canaliculus of liver cells involved in the hepatobiliary transport of organic chemicals. 

Wijnholds J, Mol CA, van Deemter L, de Haas M, Scheffer GL, Baas F, Beijnen JH, Scheper RJ, Hatse S, De Clercq E, Balzarini J, Borst P. Multi-drug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. PNAS 2000 97 7476-7481. 

Little is known of the ways of biosynthesis and insertion in the membranes of PolyP-PHB-Ca2+ complexes. In polyphosphate kinase 1 mutants of E. coli, the amounts of the complexes did not change (Castuma et al., 1995). Therefore, the PolyP in the complexes is synthesized not by polyphosphate kinase 1 but by another enzyme. E. coli strain, which lacks the AcrA component of a major multi-drug resistance pump, had greatly reduced amounts of the complexes and was defective in its ability to maintain sub-micromolar levels of free Ca2+ in the cytoplasm (Jones et al., 2003). This indicates that the AcrAB transporter may have a novel, hitherto undetected, physiological role, either directly in the membrane assembly of the PHB complexes or the transport of a component of the membrane, which is essential for assembly of the complexes into the membrane. 

Fig. 5 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. Fluorescent Compounds for the functional detection of multi drug resistance. Abbreviations CA-AM calcein AM, FL-3-AM fluo-3AM, Pot. Dyes potentiomeric dyes, RFI123 rhodaminel23, HST fioechst dye No. 33342, GS-N-PM N-Pyrenemaleimide glutathione conjugate, BOD-VER BODIPY verapamil, BOD-PRAS BODIPY prazosin, MX mitoxantrone, LYS LysoTracker dye. (Reproduced from [4])...

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