Lipophilic cations: a group of model substrates for the multidrug-resistance transporter

Gros, Philippe; Talbot, F.; Tang‐Wai, David F.; Bibi, Eitan; Hr, Kaback

doi:10.1021/bi00122a014

Cited by 80 publications

(42 citation statements)

References 37 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipophilic cations constitute a class of substrates for MDR transporters [36]. MIBI was the first radiotracer used for studying Pgp expression and inhibition.…”

Section: Discussionmentioning

confidence: 99%

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Liu

Stevenson

Barrett

et al. 2005

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Background-99m Tc-sestamibi (MIBI) and 99m Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging.Methods-Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session.Results-MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62 ± 0.15 vs. 0.55 ± 0.05, P <.05) for TF and 1.9-fold (1.21 ± 0.04 vs. 0.64 ± 0.05, P <.05) for MIBI but did not affect MCF7/WT.Conclusions-The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

show abstract

“…Lipophilic cations constitute a class of substrates for MDR transporters [36]. MIBI was the first radiotracer used for studying Pgp expression and inhibition.…”

Section: Discussionmentioning

confidence: 99%

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Liu

Stevenson

Barrett

et al. 2005

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…2): Verapamil is a calcium-channel blocker [21]. Tetraphenylphosphonium (TPP÷), a lipophylic cation, is widely used for measuring membrane potential [22]. Doxorubicin is an antineoplastic agent [21].…”

Section: A Variety Of O'totoxic Compounds Interact With Vesicular mentioning

confidence: 99%

The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters

Yelin

Schuldiner

1995

FEBS Letters

View full text Add to dashboard Cite

“…For various mammalian cells, it has been established that MDR is the result of active extrusion of drugs from the cells, a process that is catalyzed by an ATP-dependent transport protein termed P-glycoprotein or MDR1 (14). P-glycoprotein confers resistance to vinca alkaloids, anthracyclines, actinomycin D, valinomycin, gramicidin D, and phosphonium ions (4,7,9). P-glycoprotein is classified among members of the ATP-binding cassette (ABC) proteins (15) or traffic ATPases (26), to which belong prokaryotic and eukaryotic transport systems that facilitate either uptake or extrusion of substrates.…”

mentioning

confidence: 99%

Proton motive force-driven and ATP-dependent drug extrusion systems in multidrug-resistant Lactococcus lactis

et al. 1994

View full text Add to dashboard Cite

Three mutants of Lactococcus lactis subsp. lactis MG1363, termed EthR, DauR, and RhoR, were selected for resistance to high concentrations of ethidium bromide, daunomycin, and rhodamine 6G, respectively. These mutants were found to be cross resistant to a number of structurally and functionally unrelated drugs, among which were typical substrates of the mammalian multidrug transporter (P-glycoprotein) such as daunomycin, quinine, actinomycin D, gramicidin D, and rhodamine 6G. The three multidrug-resistant strains showed an increased rate of energy-dependent ethidium and daunomycin efflux compared with that of the wild-type strain. This suggests that resistance to these toxic compounds is at least partly due to active efflux. Efflux of ethidium from the EthR strain could occur against a 37-fold inwardly directed concentration gradient. In all strains, ethidium efflux was inhibited by reserpine, a well-known inhibitor of P-glycoprotein. lonophores which selectively dissipate the membrane potential or the pH gradient across the membrane inhibited ethidium and daunomycin efflux in the wild-type strain, corresponding with a proton motive force-driven efflux system. The ethidium efflux system in the EthR strain, on the other hand, was inhibited by ortho-vanadate and not upon dissipation of the proton motive force, which suggests the involvement of ATP in the energization of transport.The partial inhibition of ethidium efflux by ortho-vanadate and nigericin in the DauR and RhoR strains suggest that a proton motive force-dependent and an ATP-dependent system are expressed simultaneously. This is the first report of an ATP-dependent transport system in prokaryotes which confers multidrug resistance to the organism.Multidrug resistance (MDR) is the intrinsic or acquired resistance of cells to various structurally and functionally unrelated toxic compounds. For various mammalian cells, it has been established that MDR is the result of active extrusion of drugs from the cells, a process that is catalyzed by an ATP-dependent transport protein termed P-glycoprotein or MDR1 (14). P-glycoprotein confers resistance to vinca alkaloids, anthracyclines, actinomycin D, valinomycin, gramicidin D, and phosphonium ions (4, 7, 9). P-glycoprotein is classified among members of the ATP-binding cassette (ABC) proteins (15) or traffic ATPases (26), to which belong prokaryotic and eukaryotic transport systems that facilitate either uptake or extrusion of substrates. Because of the importance of MDR in the failure of drug-based treatment of cancers and parasital infections, most attention has been focused on eukaryotic MDR systems. Recently, however, several MDR-like systems in both gram-positive (31, 42) and gram-negative (11, 20, 23) bacteria as well as in archaea (27) have been described. The occurrence of acquired resistance in bacteria, and especially in pathogenic bacteria like enterococci, staphylococci (35), and Mycobacterium tuberculosis (3), also poses serious problems to public health. MDR in these organisms is believed to be the...

show abstract

Lipophilic cations: a group of model substrates for the multidrug-resistance transporter

Cited by 80 publications

References 37 publications

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters

Proton motive force-driven and ATP-dependent drug extrusion systems in multidrug-resistant Lactococcus lactis

Contact Info

Product

Resources

About