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of outstanding interest. A recent thorough review of genetic and molecular genetic analysis of the human P-glycoprotein. Structure - function analysis, pretranslational and postransational regulation of expression, the role of gene amplification in increased expression, and the properties of transgenic and knockout mice are discussed. In addition, the use of MDR1 as a selectable marker in the development of vectors for human gene therapy is also described.
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Gottesman MM, Hrycyna CA, Schoenlein PV, Germann UA, Pastan I. Genetic analysis of the multidrug transporter. of outstanding interest Annu Rev Genet. 29:1995;607-649 A recent thorough review of genetic and molecular genetic analysis of the human P-glycoprotein. Structure - function analysis, pretranslational and postransational regulation of expression, the role of gene amplification in increased expression, and the properties of transgenic and knockout mice are discussed. In addition, the use of MDR1 as a selectable marker in the development of vectors for human gene therapy is also described.
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Chen C-J, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 47:1986;381-389.
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Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV, Deeley RG. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 258:1992;1650-1654.
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P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake
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of outstanding interest. In this report, the authors present evidence that P-glycoprotein, under certain circumstances, may be able to transport anionic hydrophilic compounds such as methotrexate. Normally, P-glycoprotein mediates the transport of neutral or positively charged agents. The elevated level of expression of P-glycoprotein in a murine cell line that is deficient in the transport system for methotrexate results in increased resistance to methotrexate. The data in this paper and [7] show that the accumulation of methotrexate is greatly reduced in resistant cells and that resistance to methotrexate is partially reversed by a P-glycoprotein specific monoclonal antibody UIC2, suggesting that P-glycoprotein can confer resistance to methotrexate in the absence of the usual methotrexate uptake system.
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De Graaf D, Sharma RC, Mechetner EB, Schimke RT, Roninson IB. P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake. of outstanding interest Proc Natl Acad Sci USA. 93:1996;1238-1242 In this report, the authors present evidence that P-glycoprotein, under certain circumstances, may be able to transport anionic hydrophilic compounds such as methotrexate. Normally, P-glycoprotein mediates the transport of neutral or positively charged agents. The elevated level of expression of P-glycoprotein in a murine cell line that is deficient in the transport system for methotrexate results in increased resistance to methotrexate. The data in this paper and [7] show that the accumulation of methotrexate is greatly reduced in resistant cells and that resistance to methotrexate is partially reversed by a P-glycoprotein specific monoclonal antibody UIC2, suggesting that P-glycoprotein can confer resistance to methotrexate in the absence of the usual methotrexate uptake system.
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De Graaf, D.1
Sharma, R.C.2
Mechetner, E.B.3
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Roninson, I.B.5
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Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate
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Norris MD, De Graaf D, Haber M, Kavallaris M, Madafiglio J, Gilbert J, Kwan E, Stewart BW, Mechetner EB, Gudkov AV, Roninson IB. Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. Int J Cancer. 65:1996;613-619.
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Kwan, E.7
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Mechetner, E.B.9
Gudkov, A.V.10
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8
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0028867188
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Multidrug resistance proteins and other drug transport-related resistance to natural product agents
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of special interest. A review of non P-glycoprotein-mediated multidrug resistance in cancer cells. This review primarily summarizes the recent work on MRP. Expression levels in normal tissues, pharmacology, and the clinical relevance of MRP are discussed.
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Broxferman HJ, Giaccone G, Lankelma J. Multidrug resistance proteins and other drug transport-related resistance to natural product agents. of special interest Curr Opin Oncol. 7:1995;532-540 A review of non P-glycoprotein-mediated multidrug resistance in cancer cells. This review primarily summarizes the recent work on MRP. Expression levels in normal tissues, pharmacology, and the clinical relevance of MRP are discussed.
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Curr Opin Oncol
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Broxferman, H.J.1
Giaccone, G.2
Lankelma, J.3
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Transport properties of the multidrug resistance-associated protein (MRP) in human tumour cells
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Hollo Z, Homolya L, Hegedus T, Sarkadi B. Transport properties of the multidrug resistance-associated protein (MRP) in human tumour cells. FEBS Lett. 383:1996;104-990.
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Hollo, Z.1
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The role of the MDR protein in altered drug translocation across tumor cell membranes
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of outstanding interest. This review primarily focuses on the mechanism of P-glycoprotein action. The data supporting the `altered partition' model are described in great detail. The observed alterations in the electrochemical potential (intracellular pH and/or membrane potential) in a variety of multidrug resistant cells are also summarized. It should be noted, however, that it is still a matter of debate whether the alterations in electrochemical gradients are caused by the activity of P-glycoprotein or whether they result from exposing cells to drug selections for a prolonged period.
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Roepe PD. The role of the MDR protein in altered drug translocation across tumor cell membranes. of outstanding interest Biochim Biophys Acta. 1241:1995;385-405 This review primarily focuses on the mechanism of P-glycoprotein action. The data supporting the `altered partition' model are described in great detail. The observed alterations in the electrochemical potential (intracellular pH and/or membrane potential) in a variety of multidrug resistant cells are also summarized. It should be noted, however, that it is still a matter of debate whether the alterations in electrochemical gradients are caused by the activity of P-glycoprotein or whether they result from exposing cells to drug selections for a prolonged period.
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Biochim Biophys Acta
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Roepe, P.D.1
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Cornwell MM, Gottesman MM, Pastan I. Increased vinblastine binding to membrane vesicles from multidrug resistant KB cells. J Biol Chem. 262:1986;7921-7928.
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Cornwell, M.M.1
Gottesman, M.M.2
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Characterization of the azidopine and vinblastine binding site of P-glycoprotein
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Bruggemann EP, Currier SJ, Gottesman MM, Pastan I. Characterization of the azidopine and vinblastine binding site of P-glycoprotein. J Biol Chem. 267:1992;21020-21026.
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Bruggemann, E.P.1
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Ambudkar SV. Purification and reconstitution of functional human P-glycoprotein. J Bioenerg Biomembr. 27:1995;23-29.
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Lower electrical membrane potential and altered pHi homeostasis in multidrug-resistant (MDR) cells: Further characterization of a series of MDR cell lines expressing different levels of P-glycoprotein
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Roepe PD, Wei LY, Cruz J, Carlson D. Lower electrical membrane potential and altered pHi homeostasis in multidrug-resistant (MDR) cells: further characterization of a series of MDR cell lines expressing different levels of P-glycoprotein. Biochemistry. 32:1993;11042-11056.
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Carlson, D.4
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The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multi-drug transporter
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Weaver JL, Szabo G, Pine PS, Gottesman MM, Goldenberg S, Aszalos A. The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multi-drug transporter. Int J Cancer. 54:1993;456-461.
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Gupta S. New York: John Wiley and Sons
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Hrycyna CA, Zhang S, Ramachandra M, Ni B, Pastan I, Gottesman MM, Tsuruo T. Functional and molecular characterization of the human multidrug transporter. Gupta S. Multidrug Resistance in Cancer Cells: Cellular, Biochemical, Molecular and Biological Aspects. 1996;29-37 John Wiley and Sons, New York.
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Ramachandra, M.3
Ni, B.4
Pastan, I.5
Gottesman, M.M.6
Tsuruo, T.7
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0029797074
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Functional characterization of a glycine 185 to valine substitution in human P-glycoprotein using a vaccinia based transient expression system
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of outstanding interest
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Ramachandra M, Ambudkar SV, Pastan I, Gottesman MM, Hrycyna CA. Functional characterization of a glycine 185 to valine substitution in human P-glycoprotein using a vaccinia based transient expression system. of outstanding interest Mol Biol Cell. 1996;
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Pastan, I.3
Gottesman, M.M.4
Hrycyna, C.A.5
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19
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Localization of the forskolin labeling sites to both halves of P-glycoprotein: Similarity of the sites labeled by forskolin and prazosin
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Morris DI, Greenberger LM, Bruggemann EP, Cardarelli C, Gottesman MM, Pastan I, Seamon KB. Localization of the forskolin labeling sites to both halves of P-glycoprotein: similarity of the sites labeled by forskolin and prazosin. Mol Pharmacol. 46:1994;329-337.
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Pastan, I.6
Seamon, K.B.7
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Major photoaffinity drug labeling sites for iodoaryl azidoprazosin in P-glycoprotein are within, or immediately C-terminal to, transmembrane domain-6 and domain-12
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Greenberger LM. Major photoaffinity drug labeling sites for iodoaryl azidoprazosin in P-glycoprotein are within, or immediately C-terminal to, transmembrane domain-6 and domain-12. J Biol Chem. 268:1993;11417-11425.
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Raviv Y, Pollard HB, Bruggemann EP, Pastan I, Gottesman MM. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J Biol Chem. 265:1990;3975-3980.
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Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease
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Smit JJM, Schinkel AH, Oude Elferink RPJ, Groen AK, Wagenaar E, Von Deemter L, Mol CAAM, Ottenhofer R, Van der Lugt NMT, Van Roon MA, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell. 75:1993;451-462.
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Ambudkar SV, Lelong IH, Zhang JP, Cardareili CO, Gottesman MM, Pastan I. Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci USA. 89:1992;8472-8476.
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of outstanding interest. The authors describe the purification of transiently expressed human P-glycoprotein mutants containing a ten histidine tag at the carboxyl terminus by using nickel-chelate affinity chromatography. This purification protocol has enabled the authors to characterize the drug-stimulatable ATPase activity of the P-glycoprotein mutants which exhibit an altered drug-resistance phenotype. The mutations in conserved residues in the Walker A region of either the amino-terminal or carboxy-terminal ATP binding/utilization site result in the loss of drug-stimulatable ATPase activity of P-glycoprotein. Similarly, the ATPase activity of a cysteine-less mutant P-glycoprotein containing a single cysteine residue in either nucleotide-binding site is inhibited by treatment with N-ethylmalemide (see [29]). These data indicate that both ATP binding/utilization sites are essential for the hydrolysis of ATP.
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Loo TW, Clarke DM. Rapid purification of human P-glycoprotein mutants expressed transiently in HEK 293 cells by nickel-chelate chromatography and characterization of their drug-stimulated ATPase activities. of outstanding interest J Biol Chem. 270:1995;21449-21452 The authors describe the purification of transiently expressed human P-glycoprotein mutants containing a ten histidine tag at the carboxyl terminus by using nickel-chelate affinity chromatography. This purification protocol has enabled the authors to characterize the drug-stimulatable ATPase activity of the P-glycoprotein mutants which exhibit an altered drug-resistance phenotype. The mutations in conserved residues in the Walker A region of either the amino-terminal or carboxy-terminal ATP binding/utilization site result in the loss of drug-stimulatable ATPase activity of P-glycoprotein. Similarly, the ATPase activity of a cysteine-less mutant P-glycoprotein containing a single cysteine residue in either nucleotide-binding site is inhibited by treatment with N-ethylmalemide (see [29]). These data indicate that both ATP binding/utilization sites are essential for the hydrolysis of ATP. The additional findings reported on other mutants in this paper raise the interesting question of whether the level of drug-stimulatable ATPase activity of P-glycoprotein can be correlated with the extent of its ability to confer drug-resistance.
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Loo TW, Clarke DM. Covalent modification of human P-glycoprotein mutants containing a single cysteine in either nucleotide-binding fold abolishes drug-stimulated ATPase activity. J Biol Chem. 270:1995;22957-22961.
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Loo, T.W.1
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Urbatsch IL, Sankaran B, Weber J, Senior AE. P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J Biol Chem. 270:1995;19383-19390.
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of outstanding interest. This minireview summarizes recent work on the role of both ATP-binding/stimulation sites in ATP hydrolysis. A scheme for vanadate inhibition of ATP hydrolysis by P-glycoprotein is presented. In addition, the alternate catalytic site cycle of ATP hydrolysis by P-glycoprotein is presented. The proposal for the coupling of ATP hydrolysis to drug transport will facilitate further work to elucidate the role of the individual ATP-binding/utilization sites as well as of the drug-binding domain(s) in the drug transport function of P-glycoprotein.
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Senior AE, Al-Shawi MK, Urbatsch IL. The catalytic cycle of P-glycoprotein. of outstanding interest FEBS Lett. 377:1995;285-289 This minireview summarizes recent work on the role of both ATP-binding/stimulation sites in ATP hydrolysis. A scheme for vanadate inhibition of ATP hydrolysis by P-glycoprotein is presented. In addition, the alternate catalytic site cycle of ATP hydrolysis by P-glycoprotein is presented. The proposal for the coupling of ATP hydrolysis to drug transport will facilitate further work to elucidate the role of the individual ATP-binding/utilization sites as well as of the drug-binding domain(s) in the drug transport function of P-glycoprotein.
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Fine RL, Patel J, Chabner BA. Phorbol esters induce multidrug resistance in human breast cancer cells. Proc Natl Acad Sci USA. 85:1988;582-586.
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40
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Effects of phosphorylation of P-glycoprotein on multidrug resistance
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Germann UA, Chambers TC, Ambudkar SV, Pastan I, Gottesman MM. Effects of phosphorylation of P-glycoprotein on multidrug resistance. J Bioenerg Biomembr. 27:1995;53-61.
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Ambudkar, S.V.3
Pastan, I.4
Gottesman, M.M.5
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41
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Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase-C
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Chambers TC, Pohl J, Raynor RL, Kuo JF. Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase-C. J Biol Chem. 268:1993;4592-4595.
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Chambers, T.C.1
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Raynor, R.L.3
Kuo, J.F.4
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42
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Phosphorylation by protein kinse C and cyclic AMP-dependent protein kinase of synthetic peptides derived from the linker region of human P-glycoprotein
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Chambers TC, Pohl J, Glass DB, Kuo JF. Phosphorylation by protein kinse C and cyclic AMP-dependent protein kinase of synthetic peptides derived from the linker region of human P-glycoprotein. Biochem J. 299:1994;309-315.
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Chambers, T.C.1
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Kuo, J.F.4
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43
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Bacterial expression of the linker region of human MDR1 P-glycoprotein and mutational analysis of phosphorylation sites
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Chambers TC, Germann UA, Gottesman MM, Pastan I, Kuo JF, Ambudkar SV. Bacterial expression of the linker region of human MDR1 P-glycoprotein and mutational analysis of phosphorylation sites. Biochemistry. 34:1995;14156-14162.
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Chambers, T.C.1
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Gottesman, M.M.3
Pastan, I.4
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The cystic fibrosis transmembrane conductance regulator
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Riordan JR. The cystic fibrosis transmembrane conductance regulator. Annu Rev Physiol. 55:1993;609-630.
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45
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0030067789
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Characterization of phosphorylation-defective mutants of human P-glycoprotein expressed in mammalian cells
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of outstanding interest. In this paper, conclusive evidence is presented that the drug transport function and the ability of P-glycoprotein to confer drug resistance is not affected by mutations which eliminate the known sites of phosphorylation of this protein. It is shown by site-directed mutagenesis that PKA, PKC and V-1 kinase (P-glycoprotein specific kinase) phosphorylate only serine residues at positions 661, 667, 671, and 683 in the linker region of P-glycoprotein. Mutant protein lacking these four serines is not phosphorylated by PKA, PKC or V-1 kinase, ruling out the presence of additional cryptic sites elsewhere in this molecule. It is still possible that, under certain circumstances, phosphorylation - although in a subtle way - may modulate P-glycoprotein function.
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Germann UA, Chambers TC, Ambudkar SV, Licht T, Cardarelli CO, Pastan I, Gottesman MM. Characterization of phosphorylation-defective mutants of human P-glycoprotein expressed in mammalian cells. of outstanding interest J Biol Chem. 271:1996;1708-1716 In this paper, conclusive evidence is presented that the drug transport function and the ability of P-glycoprotein to confer drug resistance is not affected by mutations which eliminate the known sites of phosphorylation of this protein. It is shown by site-directed mutagenesis that PKA, PKC and V-1 kinase (P-glycoprotein specific kinase) phosphorylate only serine residues at positions 661, 667, 671, and 683 in the linker region of P-glycoprotein. Mutant protein lacking these four serines is not phosphorylated by PKA, PKC or V-1 kinase, ruling out the presence of additional cryptic sites elsewhere in this molecule. It is still possible that, under certain circumstances, phosphorylation - although in a subtle way - may modulate P-glycoprotein function.
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(1996)
J Biol Chem
, vol.271
, pp. 1708-1716
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Germann, U.A.1
Chambers, T.C.2
Ambudkar, S.V.3
Licht, T.4
Cardarelli, C.O.5
Pastan, I.6
Gottesman, M.M.7
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46
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0027005480
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Activation of MDR1 (P-glycoprotein) gene expression in human cells by protein kinase-C agonists
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Chaudhary PM, Roninson IB. Activation of MDR1 (P-glycoprotein) gene expression in human cells by protein kinase-C agonists. Oncol Res. 4:1992;281-290.
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Chaudhary, P.M.1
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47
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Functional role of phosphorylation of the multidrug transporter (P-glycoprotein) by protein kinase C in multidrug-resistant MCF-7 cells
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Aftab DT, Yang JM, Hait WN. Functional role of phosphorylation of the multidrug transporter (P-glycoprotein) by protein kinase C in multidrug-resistant MCF-7 cells. Oncol Res. 6:1994;59-70.
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Aftab, D.T.1
Yang, J.M.2
Hait, W.N.3
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48
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0029181956
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Volume-activated chloride currents associated with the multidrug resistance P-glycoprotein
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of special interest. This review summarizes the work on volume-activated chloride channel activity associated with P-glycoprotein. Both the views - including the earlier one proposing that P-glycoprotein itself is a chloride channel and the more recent observations (see [51]) suggesting that it is instead a regulator of the volume-activated chloride channel activity - are covered. The role of P-glycoprotein as either a chloride channel or its modulator, however, is still very controversial (see also [52]).
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Higgins CF. Volume-activated chloride currents associated with the multidrug resistance P-glycoprotein. of special interest J Physiol (Lond). 482:1995;31S-36S This review summarizes the work on volume-activated chloride channel activity associated with P-glycoprotein. Both the views - including the earlier one proposing that P-glycoprotein itself is a chloride channel and the more recent observations (see [51]) suggesting that it is instead a regulator of the volume-activated chloride channel activity - are covered. The role of P-glycoprotein as either a chloride channel or its modulator, however, is still very controversial (see also [52]).
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(1995)
J Physiol (Lond)
, vol.482
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Higgins, C.F.1
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49
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0029049154
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Effects of hypotonic and hypoionic media on drug pumping by P-glycoprotein expressed in epithelial and nonepithelial cell lines
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Ambasch K, Cabantchik ZI, Slotki IN. Effects of hypotonic and hypoionic media on drug pumping by P-glycoprotein expressed in epithelial and nonepithelial cell lines. J Cell Physiol. 164:1995;117-122.
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J Cell Physiol
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Ambasch, K.1
Cabantchik, Z.I.2
Slotki, I.N.3
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50
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0030014951
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MDR1/P-glycoprotein function. I. Effect of hypotonicity and inhibitors of rhodamine 123 exclusion
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(Cell Physiol 39)
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Weaver JL, McKinney L, Schoenlein PV, Goldenberg S, Gottesman MM, Aszalos A. MDR1/P-glycoprotein function. I. Effect of hypotonicity and inhibitors of rhodamine 123 exclusion. Am J Physiol. 270(Cell Physiol 39):1996;C1447-C1452.
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(1996)
Am J Physiol
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Weaver, J.L.1
McKinney, L.2
Schoenlein, P.V.3
Goldenberg, S.4
Gottesman, M.M.5
Aszalos, A.6
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51
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0028876622
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Protein kinase C-mediated phosphorylation of the human multidrug resistance P-glycoprotein regulates cell volume-activated chloride channels
-
of special interest. In this article, evidence is presented that P-glycoprotein itself does not function as a volume-activated chloride channel; instead, the phosphorylation of P-glycoprotein by PKC regulates the activity of an endogenous chloride channel. The role of PKC mediated phosphorylation is confirmed by the mutagenesis of serine and threonine residues in the consensus phosphorylation sites in the linker region of P-glycoprotein.
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Hardy SP, Goodfellow HR, Valverde MA, Gill DR, Sepulveda V, Higgins CF. Protein kinase C-mediated phosphorylation of the human multidrug resistance P-glycoprotein regulates cell volume-activated chloride channels. of special interest EMBO J. 14:1995;68-75 In this article, evidence is presented that P-glycoprotein itself does not function as a volume-activated chloride channel; instead, the phosphorylation of P-glycoprotein by PKC regulates the activity of an endogenous chloride channel. The role of PKC mediated phosphorylation is confirmed by the mutagenesis of serine and threonine residues in the consensus phosphorylation sites in the linker region of P-glycoprotein.
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(1995)
EMBO J
, vol.14
, pp. 68-75
-
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Hardy, S.P.1
Goodfellow, H.R.2
Valverde, M.A.3
Gill, D.R.4
Sepulveda, V.5
Higgins, C.F.6
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52
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0028807094
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Volume-sensitive chloride channel activity does not depend on endogenous P-glycoprotein
-
of special interest. Evidence is presented here that endogenously expressed P-glycoprotein in a human small intestinal epithelial cell line neither functions as a volume-activated chloride channel nor as a PKC mediated modulator of the chloride channel. The volume-activated chloride channel activity is not inhibited by P-glycoprotein specific antibodies or by its substrates and modulators. These findings, thus, bring into question the proposed association of P-glycoprotein with the chloride channel.
-
Tominaga M, Tominaga T, Miwa A, Okada Y. Volume-sensitive chloride channel activity does not depend on endogenous P-glycoprotein. of special interest J Biol Chem. 270:1995;27887-27893 Evidence is presented here that endogenously expressed P-glycoprotein in a human small intestinal epithelial cell line neither functions as a volume-activated chloride channel nor as a PKC mediated modulator of the chloride channel. The volume-activated chloride channel activity is not inhibited by P-glycoprotein specific antibodies or by its substrates and modulators. These findings, thus, bring into question the proposed association of P-glycoprotein with the chloride channel.
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(1995)
J Biol Chem
, vol.270
, pp. 27887-27893
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Tominaga, M.1
Tominaga, T.2
Miwa, A.3
Okada, Y.4
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53
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0027475309
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The multidrug resistance (mdr1) gene product functions as an ATP channel
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Abraham EH, Prat AG, Gerweck L, Seneveratne T, Arceci RJ, Kramer R, Guidotti G, Cantiello HF. The multidrug resistance (mdr1) gene product functions as an ATP channel. Proc Natl Acad Sci USA. 90:1993;312-316.
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(1993)
Proc Natl Acad Sci USA
, vol.90
, pp. 312-316
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Abraham, E.H.1
Prat, A.G.2
Gerweck, L.3
Seneveratne, T.4
Arceci, R.J.5
Kramer, R.6
Guidotti, G.7
Cantiello, H.F.8
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54
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0029998981
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Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP
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Reddy MM, Quinton PM, Haws C, Wine JJ, Grygorczyk R, Tabcharani JA, Hanrahan JW, Gunderson KL, Kopito RR. Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP. Science. 271:1996;1876-1879.
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(1996)
Science
, vol.271
, pp. 1876-1879
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Reddy, M.M.1
Quinton, P.M.2
Haws, C.3
Wine, J.J.4
Grygorczyk, R.5
Tabcharani, J.A.6
Hanrahan, J.W.7
Gunderson, K.L.8
Kopito, R.R.9
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55
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0027218689
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Biochemistry of multidrug resistance mediated by the multidrug transporter
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Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 62:1993;385-427.
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(1993)
Annu Rev Biochem
, vol.62
, pp. 385-427
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Gottesman, M.M.1
Pastan, I.2
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56
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0028229150
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Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
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Schinkel AH, Smit JJ, Van Tellingen O, Beijnen JH, Wagenaar E, Van Deemter L, Mol CA, Van der Valk MA, Robanus-Maandag EC, Te Riele HP, et al. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 77:1994;491-502.
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(1994)
Cell
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Schinkel, A.H.1
Smit, J.J.2
Van Tellingen, O.3
Beijnen, J.H.4
Wagenaar, E.5
Van Deemter, L.6
Mol, C.A.7
Van der Valk, M.A.8
Robanus-Maandag, E.C.9
Te Riele, H.P.10
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57
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0028825399
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Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A
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Schinkel AH, Wagenaar E, Van Deemter L, Mol CA, Borst P. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest. 96:1995;1698-1705.
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(1995)
J Clin Invest
, vol.96
, pp. 1698-1705
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Schinkel, A.H.1
Wagenaar, E.2
Van Deemter, L.3
Mol, C.A.4
Borst, P.5
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58
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0026487058
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Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone
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Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem. 267:1992;24248-24252.
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(1992)
J Biol Chem
, vol.267
, pp. 24248-24252
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Ueda, K.1
Okamura, N.2
Hirai, M.3
Tanigawara, Y.4
Saeki, T.5
Kioka, N.6
Komano, T.7
Hori, R.8
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59
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0028543657
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Expression of the mdr1 P-glycoprotein gene: A mechanism of escape from glucocorticoid-induced apoptosis
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Gruol DJ, Bourgeois S. Expression of the mdr1 P-glycoprotein gene: a mechanism of escape from glucocorticoid-induced apoptosis. Biochem Cell Biol. 72:1994;561-571.
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(1994)
Biochem Cell Biol
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Gruol, D.J.1
Bourgeois, S.2
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60
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0027733657
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Targeted disruption of the mouse mdr1b gene reveals that steroid hormones enhance mdr gene expression
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Altuvia S, Stein WD, Goldenberg S, Kane SE, Pastan I, Gottesman MM. Targeted disruption of the mouse mdr1b gene reveals that steroid hormones enhance mdr gene expression. J Biol Chem. 268:1993;27127-27132.
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(1993)
J Biol Chem
, vol.268
, pp. 27127-27132
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Altuvia, S.1
Stein, W.D.2
Goldenberg, S.3
Kane, S.E.4
Pastan, I.5
Gottesman, M.M.6
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61
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0029013333
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LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones
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Kralli A, Bohe SP, Yamamoto KR. LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones. Proc Natl Acad Sci USA. 92:1995;4701-4705.
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(1995)
Proc Natl Acad Sci USA
, vol.92
, pp. 4701-4705
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Kralli, A.1
Bohe, S.P.2
Yamamoto, K.R.3
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62
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0029981430
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Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene
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of special interest. This article reports the presence of a multiorganic anion transporter, MOAT, in the canalicular (apical) membranes of rat hepatocytes. The rat MOAT is a liver-specific homolog of human MRP and is involved in the hepatobiliary secretion of bilirubin glucuronides and other conjugated organic anions.
-
Paulusma CC, Bosma PJ, Zaman GJR, Bakker CTM, Otter M, Scheffer GL, Scheper RJ, Borst P, Oude Elferink RP. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. of special interest Science. 271:1996;1126-1128 This article reports the presence of a multiorganic anion transporter, MOAT, in the canalicular (apical) membranes of rat hepatocytes. The rat MOAT is a liver-specific homolog of human MRP and is involved in the hepatobiliary secretion of bilirubin glucuronides and other conjugated organic anions.
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(1996)
Science
, vol.271
, pp. 1126-1128
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-
Paulusma, C.C.1
Bosma, P.J.2
Zaman, G.J.R.3
Bakker, C.T.M.4
Otter, M.5
Scheffer, G.L.6
Scheper, R.J.7
Borst, P.8
Oude Elferink, R.P.9
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63
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0029013159
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P-glycoprotein and pharmacokinetics
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Leveque D, Jehl F. P-glycoprotein and pharmacokinetics. Anticancer Res. 15:1995;331-336.
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(1995)
Anticancer Res
, vol.15
, pp. 331-336
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Leveque, D.1
Jehl, F.2
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64
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0029028792
-
Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: Implications for drug delivery and activity in cancer chemotherapy
-
of outstanding interest. This review deals with the overlapping tissue distribution and substrate specificities of P-glycoproteins and cytochrome P450 3A. Several tumor samples show a concomitant increase in expression of P-glycoprotein as well as isozyme 3A of cytochrome P450. Several anticancer hydrophobic drugs, calcium channel blockers, flavonoids, immunosuppressive agents and hormones, such as dexamethasone, hydrocortisone and progesterone, exhibit affinity toward both proteins. The similarities in drug recognition between P-glycoprotein and cytochrome P450 3A are not widely recognized. They do, however, present unique challenges in understanding pharmacokinetics of drug absorption, metabolism and excretion.
-
Wacher VJ, Wu CY, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. of outstanding interest Mol Carcinog. 13:1995;129-134 This review deals with the overlapping tissue distribution and substrate specificities of P-glycoproteins and cytochrome P450 3A. Several tumor samples show a concomitant increase in expression of P-glycoprotein as well as isozyme 3A of cytochrome P450. Several anticancer hydrophobic drugs, calcium channel blockers, flavonoids, immunosuppressive agents and hormones, such as dexamethasone, hydrocortisone and progesterone, exhibit affinity toward both proteins. The similarities in drug recognition between P-glycoprotein and cytochrome P450 3A are not widely recognized. They do, however, present unique challenges in understanding pharmacokinetics of drug absorption, metabolism and excretion.
-
(1995)
Mol Carcinog
, vol.13
, pp. 129-134
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-
Wacher, V.J.1
Wu, C.Y.2
Benet, L.Z.3
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65
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0029945113
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What have we learnt thus far from mice with disrupted P-glycoprotein genes?
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Borst P, Schinkel AH. What have we learnt thus far from mice with disrupted P-glycoprotein genes? Eur J Cancer. 32:1996;985-990.
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(1996)
Eur J Cancer
, vol.32
, pp. 985-990
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Borst, P.1
Schinkel, A.H.2
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