Kinetics of the multidrug transporter (P-glycoprotein) and its reversal

Physiological Reviews

Volumn 77, Issue 2, 1997, Pages 545-590

  Stein, Wilfred D ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE KINASE; AZIDE; CYTOTOXIN; DAUNORUBICIN; GLYCOPROTEIN P; PROPAFENONE; TRIFLUOPERAZINE; VERAPAMIL; VINBLASTINE;

ARTICLE; BINDING SITE; CANCER MORTALITY; CELL KILLING; CELL MEMBRANE TRANSPORT; CONFORMATIONAL TRANSITION; DIFFUSION; DRUG TRANSPORT; DRUG UPTAKE; ION TRANSPORT; MULTIDRUG RESISTANCE; PHOTOAFFINITY LABELING; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; SOLUBILITY; STRUCTURE ACTIVITY RELATION; TRANSPORT KINETICS;

EID: 0030966409     PISSN: 00319333     EISSN: None     Source Type: Journal    
DOI: 10.1152/physrev.1997.77.2.545     Document Type: Article

References (260)

1. ABRAHAM, E. H., A. G. PRAT, L. GERWECK, T. SENEVERATNE, R. J. ARCECI, R. KRAMER, G. GUIDOTTI, AND H. F. CANTIELLO. The multidrug resistance (mdr1) gene product functions as an ATP channel. Proc. Natl. Acad. Sci. USA 90: 312-316, 1993.
2. AL-AWQATI, Q. Regulation of ion channels by ABC transporters that secrete ATP. Science Wash. DC 269: 805-806, 1995.
3. ALLEN, L. M. Comparison of uptake and binding of two epipodophyllotoxin glucopyranosides, 4′-demethyl epipodophyllotoxin thenylidene-beta-D-glucoside and 4′-demethyl epipodophyllotoxin ethylidene-beta-D-glucFDoside, in the L1210 leukemia cell. Cancer Res. 38: 2549-2554, 1978.
4. r 190,000 multidrug resistance protein (MRP) in drug-selected and transfected human tumor cells. Cancer Res. 55: 102-110, 1995.
5. AL-SHAWI, M. K., AND A. E. SENIOR. Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein. J. Biol. Chem. 268: 4197-4206, 1993.
6. AL-SHAWI, M. K., I. L. URBATSCH, AND A. E. SENIOR. Covalent inhibitors of P-glycoprotein ATPase activity. J. Biol. Chem. 269: 8986-8992, 1994.
7. ALTENBERG, G. A., C. G. VANOYE, J. K. HORTON, AND L. REUSS. Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: evidence against direct drug extrusion from the plasma membrane. Proc. Natl. Acad. Sci. USA 91: 4654-4657, 1994.
8. ALVAREZ, M., K. PAULL, A. MONKS, C. HOSE, J.-S. LEE, J. WEINSTEIN, M. GREVER, AND S. BATES. Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute anticancer drug screen. J. Clin. Invest. 95: 2205-2214, 1995.
9. AMBUDKAR, S. H., I. H. LELONG, J. ZHANG, C. O. CARDARELLI, M. M. GOTTESMAN, AND I. PASTAN. Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc. Natl. Acad. Sci. USA 89: 8472-8476, 1992.
10. ARVELO, F., M. F. POUPON, F. BICHAT, F. GROSSIN, Y. BOURGEOIS, M. JACROT, G. BASTIAN, AND T. LE CHEVALIER. Adding a reverser (verapamil) to combined chemotherapy overrides resistance in small cell lung cancer xenografts. Eur. J. Cancer 31: 1862-1868, 1995.
11. AYESH, S., E. LYUBIMOV, N. ALGOUR, AND W. D. STEIN. Reversal of P-glycoprotein is greatly reduced by the presence of plasma but can be monitored by an ex vivo clinical assay. Anticancer Drugs 7: 678-686, 1996.
12. AYESH, S., Y.-M. SHAO, AND W. D. STEIN. Co-operative, competitive and non-competitive interactions between modulators of P-glycoprotein. Biochim. Biophys. Acta 1316: 8-18, 1996.
13. AZZARIA, M., E. SCHURR, AND P. GROS. Discrete mutations introduced in the predicted nucleotide-binding sites of the mdr1 gene abolish its ability to confer multidrug resistance. Mol. Cell. Biol. 9: 5289-5297, 1989.
14. BAAS, F., AND P. BORST. The tissue dependent expression of hamster P-glycoprotein genes. FEBS Lett. 229: 329-332, 1988.
15. BALDINI, N., K. SCOTLANDI, G. BARBANTI RODANO, M. C. MANARA, D. MAURICI, G. BACCI, F. BERTONI, P. PICCI, S. SOTTILI, AND M. CAMPANACCI. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N. Engl. J. Med. 333: 1380-1385, 1995.
16. BATES, S. E., B. MEADOWS, B. R. GOLDSPIEL, A. DENICOFF, T. B. LE, E. TUCKER, S. M. STEINBERG, AND L. J. ELWOOD. A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer. Cancer Chemother. Pharmacol. 35: 457-463, 1995.
17. - channel gating to an ATP hydrolysis cycle. Neuron 12: 473-482, 1994.
18. BEJA, O., AND E. BIBI. Multidrug resistance protein (Mdr)-alkaline phosphatase hybrids in Escherichia coli suggest a major revision in the topology of the C-terminal half of Mdr. J. Biol. Chem. 270: 12351-12354, 1995.
19. BIBI, E., AND O. BEJA. Membrane topology of multidrug resistance protein expressed in Escherichia coli N-terminal domain. J. Biol. Chem. 269: 19910-19915, 1994.
20. BIBI, E., P. GROSS, AND H. R. KABACK. Functional expression of mouse mdr1 in Escherichia coli. Proc. Natl. Acad. Sci. USA 90: 9209-9213, 1993.
21. BIEDLER, J. L., AND H. RIEHM. Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic, and cytogenetic studies. Cancer Res. 30: 1174-1184, 1970.
22. BORGNIA, M. J., G. D. EYTAN, AND Y. G. ASSARAF. Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J. Biol. Chem. 271: 3163-3171, 1996.
23. BORNMANN, W. G., AND P. D. ROEPE. Analysis of drug transport kinetics in multidrug-resistant cells using a novel coumarin-viblastine compound. Biochemistry 33: 12665-12675, 1994.
24. BOSCOBOINIK, D., R. S. GUPTA, AND R. M. EPAND. Investigation of the relationship between altered intracellular pH and multidrug resistance in mammalian cells. Br. J. Cancer 61: 568-572, 1990.
25. BRENNER, B. Rapid dissociation and reassociation of actomyosin cross-bridges during force generation: a newly observed facet of cross-bridge action in muscle. Proc. Natl. Acad. Sci. USA 88: 10490-10494, 1991.
26. BREUNINGER, L. M., S. PAUL, K. GAUGHAN, T. MIKI, A. CHAN, S. A. AARONSON, AND G. D. KRUH. Expression of multidrug-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. Cancer Res. 55: 5342-5347, 1995.
27. BRISMAR, T., A. GRUBER, AND C. PETERSON. Increased cation transport in mdr1-gene-expressing K562 cells. Cancer Chemother. Pharmacol. 36: 87-90, 1995.
28. BROXTERMAN, H. J., H. M. PINEDO, G. J. SCHUURHUIS, AND J. LANKELMA. Cyclosporin A and verapamil have different effects on energy metabolism in multidrug-resistant tumour cells. Br. J. Cancer 62: 85-88, 1990.
29. BRUGGEMANN, E. P., S. J. CURRIER, M. M. GOTTESMAN, AND I. PASTAN. Characterization of the azidopine and vinblastine binding site of P-glycoprotein. J. Biol. Chem. 267: 21020-21026, 1992.
30. CAMPOS, L., D. GUYOTAT, E. ARCHIMBAUD, P. CALMARD RIOL, T. TSURUO, J. TRONCY, D. TREILLE, AND D. FIBRE. Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79: 473-476, 1992.
31. CANO-GAUCI, D. F., R. BUSCHE, B. TUMMLER, AND J. R. RIORDAN. Fast kinetic analysis of drug transport in multidrug resistant cells using a pulsed quench-flow apparatus. Biochem. Biophys. Res. Commun. 167: 48-53, 1990.
32. CARDARELLI, C. O., I. AKSENTIJEVICH, I. PASTAN, AND M. M. GOTTESMAN. Differential effects of P-glycoprotein inhibitors on NIH3T3 cells transfected with wild-type (G185) or mutant (V185) multidrug transporters. Cancer Res. 55: 1086-1091, 1995.
33. CHAMBERS, T. C., U. A. GERMANN, M. M. GOTTESMAN, I. PASTAN, J. F. KUO, AND S. H. AMBUDKAR. Bacterial expression of the linker region of human MDR1 P-glycoprotein and mutational analysis of phosphorylation sites. Biochemistry 34: 14156-14162, 1995.
34. CHAMBERS, T. C., E. M. McAVOY, J. W. JACOBS, AND G. EILON. Protein kinase C phosphorylates P-glycoprotein in multidrug resistant human KB carcinoma cells. J. Biol. Chem. 265: 7679-7686, 1990.
35. CHAMBERS, T. C., J. POHL, R. L. RAYNOR, AND J. F. KUO. Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase C. J. Biol Chem. 268: 4592-4595, 1993.
36. CHAN, H. S., G. HADDAD, P. S. THORNER, G. DEBOER, Y. P. LIN, N. ONDRUSEK, H. YEGER, AND V. LING. P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N. Engl. J. Med. 325: 1608-1614, 1991.
37. CHEN, C.-I., J. E. CHIN, K. UEDA, D. P. CLARK, I. PASTAN, M. M. GOTTESMAN, AND I. B. RONINSON. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47: 381-389, 1986.
38. CHEN, G., J. P. JAFFREZOU, W. H. FLEMING, G. E. DURAN, AND B. I. SIKIC. Prevalence of multidrug resistance related to activation of the mdr1 gene in human sarcoma mutants derived by single-step doxorubicin selection. Cancer Res. 54: 4980-4987, 1994.
39. CHILDS, S., R. L. YEH, E. GEORGES, AND V. LING. Identification of a sister gene to P-glycoprotein. Cancer Res. 55: 2029-2034, 1995.
40. CHOI, K., C.-J. CHEN, M. KRIEGLER, AND I. B. RONINSON. An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell 53: 519-529, 1988.
41. CHRISTEN, R. D., E. F. McCLAY, S. C. PLAXE, S. S. YEN, S. KIM, S. KIRMANI, L. L. WILGUS, D. D. HEATH, D. R. SHALINSKY, AND J. L. FREDDO. Phase I/pharmacokinetic study of high-dose progesterone and doxorubicin. J. Clin. Oncol. 11: 2417-2426, 1993.
42. COLLANDER, R. The permeability of Nitella cells to nonelectrolytes. Physiol. Plant 7: 420-445, 1954.
43. CONNOR, J., C. H. PAK, R. F. A. ZWAAL, AND A. J. SCHROIT. Bidirectional transbilayer movement of phospholipid analogs in human red blood cells: evidence for an ATP-dependent and protein-mediated process. J. Biol. Chem. 267: 19412-19417, 1992.
44. DALMARK, M., AND E. K. HOFFMAN. Doxorubicin (Adriamycin) transport in Ehrlich ascites tumour cells: comparison with transport in human red blood cells. Scand. J. Clin. Lab. Invest. 43: 241-248, 1983.
45. DALMARK, M. Characteristics of doxorubicin transport in human red blood cells. Scand. J. Clin. Lab. Invest. 41: 633-639, 1981.
46. DALMARK, M., AND H. H. STORM. A Fickian diffusion transport process with features of transport catalysis - doxorubicin transport in human red blood cells. J. Gen. Physiol. 78: 349-364, 1981.
47. DALTON, W. S. Drug resistance modulation in the laboratory and the clinic. Semin. Oncol. 20: 64-69, 1993.
48. DALTON, W. S., T. M. GROGAN, P. S. MELTZER, R. J. SCHEPER, B. G. DURIE, C. W. TAYLOR, T. P. MILLER, AND S. E. SALMON. Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J. Clin. Oncol. 7: 415-424, 1989.
49. DAMIANI, D., M. MICHIELI, A. MICHELUTTI, R. FANIN, D. RUSSO, AND M. BACCARANI. P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia. Leuk. Lymphoma 17: 289-294, 1995.
50. DANO, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim. Biophys. Acta 323: 466-483, 1973.
51. DEAN, M., R. ALLIKMETS, B. GERRARD, C. STEWART, A. KISTLER, B. SHAFER, S. MICHAELIS, AND J. STRATHERN. Mapping and sequencing of two yeast genes belonging to the ATP-binding casette superfamily. Yeast 10: 377-383, 1994.
52. DEMANT, E. J. F., M. SEHESTED, AND P. B. JENSEN. A model for computer simulation of P-glycoprotein and transmembrane pH-mediated anthracycline transport in multidrug-resistant tumor cells. Biochim. Biophys. Acta 1055: 117-125, 1990.
53. DEVINE, S. E., V. LING, AND P. W. MELERA. Amino acid substitutions in the sixth transmembrane domain of P-glycoprotein alter multidrug resistance. Proc. Natl. Acad. Sci. USA 89: 4564-4568, 1992.
54. DEVINE, S. E., AND P. W. MELERA. Diversity of multidrug resistance in mammalian cells. J. Biol. Chem. 269: 6133-6139, 1994.
55. DIDIER, A. D., J. WENGER, AND F. LOOR. Decreased uptake of cyclosporin A by P-glycoprotein (Pgp) expressing CEM leukemic cells and restoration of normal retention by Pgp blockers. Anticancer Drugs 6: 669-680, 1995.
56. DOIGE, C. A., AND G. F. AMES. ATP-dependent transport systems in bacteria and humans: relevance to cystic fibrosis and multidrug resistance. Annu. Rev. Microbiol. 47: 291-319, 1993.
57. DOIGE, C. A., AND F. J. SHAROM. Transport properties of P-glycoprotein in plasma membrane vesicles from multidrug-resistant Chinese hamster ovary cells. Biochim. Biophys. Acta 1109: 161-171, 1992.
58. DORDAL, M. S., J. N. WINTER, AND A. J. ATKINSON. Kinetic analysis of P-glycoprotein-mediated doxorubicin efflux. J. Pharmacol. Exp. Ther. 263: 762-766, 1992.
59. DRORI, S., G. D. EYTAN, AND Y. G. ASSARAF. Potentiation of anticancer-drug cytotoxicity by multidrug-resistance chemosensitizers involves alterations in membrane fluidity leading to increased membrane permeability. Eur. J. Biochem. 228: 1020-1029, 1995.
60. EGORIN, M. J., S. W. SNYDER, S.-S. PAN, AND C. DALY. Cellular transport and accumulation of thiotepa in murine, human, and avian cells. Cancer Res. 49: 5611-5617, 1989.
61. EHRING, G. R., Y. V. OSIPCHUK, AND M. D. CAHALAN. Swelling-activated chloride channels in multidrug-sensitive and -resistant cells. J. Gen. Physiol. 104: 1129-1161, 1994.
62. EKSBORG, S., H. EHRSSON, AND B. EKQVIST. Protein binding of anthraquinone glycosides, with special reference to adriamycin. Cancer Chemother. Pharmacol. 10: 7-10, 1982.
63. ENDICOTT, J. A., AND V. LING. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 58: 137-171, 1989.
64. EYTAN, G. D., M. J. BORGNIA, R. REGEV, AND Y. G. ASSARAF. Transport of polypeptide ionophores into proteoliposomes reconstituted with rat liver P-glycoprotein. J. Biol. Chem. 269: 26058-26065, 1994.
65. EYTAN, G. D., R. REGEV, AND Y. G. ASSARAF. Functional reconstitution of P-glyccoprotein reveals an apparent near stoichiometric drug transport to ATP hydrolysis. J. Biol. Chem. 271: 3172-3178, 1996.
66. EYTAN, G. D., R. REGEV, G. OREN, AND Y. G. ASSARAF. The role of passive transbilayer drug movement in multidrug resistance and its modulation. J. Biol. Chem. 271: 12897-12902, 1996.
67. FOJO, A., S.-I. AKIYAMA, M. M. GOTTESMAN, AND I. PASTAN. Reduced drug accumulation in multiply drug-resistant human KB carcinoma cell lines. Cancer Res. 45: 3002-3007, 1985.
68. FORD, J. M., E. P. BRUGGEMANN, I. PASTAN, M. M. GOTTESMAN, AND W. N. HAIT. Cellular and biochemical characterization of thioxanthenes for reversal of multidrug resistance in human and murine cell lines. Cancer Res. 50: 1748-1756, 1990.
69. FORD, J. M., AND W. N. HAIT. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol. Rev. 42: 155-199, 1990.
70. FORD, J. M., W. C. PROZIALECK, AND W. N. HAIT. Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance. Mol. Pharmacol. 35: 105-115, 1989.
71. FREZARD, F., AND A. GARNIER-SUILLEROT. Comparison of the membrane transport of anthracycline derivatives in drug-resistant and drug-sensitive K562 cells. Eur. J. Biochem. 196: 483-491, 1991.
72. FRICHE, E., P. B. JENSEN, H. ROED, T. SKOVSGAARD, AND N. I. NISSEN. In vitro circumvention of anthracycline-resistance in Ehrlich ascites tumour by anthracycline analogues. Biochem. Pharmacol. 39: 1721-1726, 1990.
73. GANAPATHI, R., AND D. GRABOWSKI. Differential effect of the calmodulin inhibitor trifluoroperazine in modulating cellular accumulation, retention and cytotoxicity of doxorubicin-resistant L1210. Biochem. Pharmacol. 37: 185-193, 1988.
74. GARRIGOS, M., J. J. BELEHRADEK, L. M. MIR, AND S. ORLOWSKI. Absence of cooperativity for MgATP and verapamil effects on the ATPase activity of P-glycoprotein containing membrane vesicles. Biochem. Biophys. Res. Commun. 196: 1034-1041, 1993.
75. 74a. GHAUHARALI, R. I., H. V. WESTERHOFF, H. DEKKER, AND J. LANKELMA. Saturable P-glycoprotein kinetics assayed by fluorescence studies of drug efflux from suspended human KB8-5 cells. Biochim. Biophys. Acta 1278: 213-222, 1996.
76. GOTTESMAN, M. M., AND I. PASTAN. The multidrug transporter, a double-edged sword. J. Biol. Chem. 263: 12163-12166, 1988.
77. GOTTESMAN, M. M., AND I. PASTAN. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62: 385-427, 1993.
78. GRECO, W. R., G. BRAVO, AND J. C. PARSONS. The search for synergy: a critical review from a response surface perspective. Pharmacol. Rev. 47: 331-385, 1995.
79. GREIG, N. H., T. T. SONCRANT, H. U. SHETTY, AND S. MOMMA. Brain uptake and anticancer activities of vincristine and vinblastine are restricted by their low cerebrovascular permeability and binding to plasma constituents in rat. Cancer Chemother. Pharmacol. 26: 263-268, 1990.
80. GROS, P., AND E. BUSCHMAN. The mouse multidrug resistance gene family: structural and functional analysis. Int. Rev. Cytol. 137: 169-197, 1993.
81. GROS, P., J. CROOP, AND D. HOUSMAN. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47: 371-380, 1986.
82. GROS, P., R. DHIR, J. CROOP, AND F. TALBOT. A single amino acid substitution strongly modulates the activity and substrate specificity of the mouse mdr1 and mdr3 drug efflux pumps. Proc. Natl. Acad. Sci. USA 88: 7289-7293, 1991.
83. GROS, P., F. TALBOT, D. TANG-WAI, E. BIBI, AND H. R. KABACK. Lipophilic cations - a group of model substrates for the multidrug-resistance transporter. Biochemistry 31: 1992-1998, 1992.
84. GUNDERSON, K. L., AND R. R. KOPITO. Conformational states of CFTR associated with channel gating: the role of ATP binding and hydrolysis. Cell 82: 231-239, 1995.
85. HABER, M., C. A. BURKHART, D. L. REGL, J. MADAFIGLIO, M. D. NORRIS, AND S. B. HORWITZ. Altered expression of M beta 2, the class II beta-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance. J. Biol. Chem. 270: 31269-31275, 1995.
86. HE, X. M., AND D. C. CARTER. Atomic structure and chemistry of human serum albumin. Nature Lond. 358: 209-215, 1992.
87. HEICHAL, O., D. ISH-SHALOM, R. KOREN, AND W. D. STEIN. The kinetic dissection of transport from metabolic trapping during substrate uptake by intact cells: uridine uptake by quiescent and serum-activated NIL 8 hamster cells and their murine sarcoma virus-transformed counterparts. Biochim. Biophys. Acta 551: 169-186, 1979.
88. HEMPLING, H. G. Application of irreversible thermodynamics to a functional description of the tumor cell membrane. J. Gen. Physiol. 70: 237-256, 1968.
89. HEMPLING, H. G. Permeability of the Ehrlich ascites cell to water. J. Gen. Physiol. 44: 365-379, 1960.
90. HERMAN, L. W., V. SHARMA, J. F. KRONAUGE, E. BARBARICS, L. A. HERMAN, AND D. PIWNICA-WORMS. Novel hexakis(arene-isonitrile)technetium(I) complexes as radioligands targeted to the multidrug resistance P-glycoprotein. J. Med. Chem. 38: 2955-2963, 1995.
91. HIGGINS, C. F. The multidrug resistance P-glycoprotein. Curr. Opin. Cell Biol. 5: 684-687, 1993.
92. HIGGINS, C. F. The ABC of channel regulation. Cell 82: 693-696, 1995.
93. HIGGINS, C. F., AND M. M. GOTTESMAN. Is the multidrug transporter a flippase. Trends Biochem. Sci. 17: 18-21, 1992.
94. HOLLO, Z., L. HOMOLYA, C. W. DAVIS, AND B. SARKADI. Calcein accumulation as a fluorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta 1191: 384-388, 1994.
95. HOLMES, J. A., AND R. R. WEST. The effect of MDR-1 gene expression on outcome in acute myeloblastic leukemia. Br. J. Cancer 69: 382-384, 1994.
96. HOMOLYA, L., Z. HOLLO, U. A. GERMANN, I. PASTAN, M. M. GOTTESMAN, AND B. SARKADI. Fluorescent cellular indicators are extruded by the multidrug resistance protein. J. Biol. Chem. 268: 21493-21496, 1993.
97. 3H]vinblastine transport by isolated vesicles. Biochim. Biophys. Acta 1061: 106-110, 1991.
98. HOSKING, L. K., R. D. WHELAN, S. A. SHELLARD, S. L. DAVIES, I. D. HICKSON, M. K. DANKS, AND B. T. HILL. Multiple mechanisms of resistance in a series of human testicular teratoma cell lines selected for increasing resistance to etoposide. Int. J. Cancer 57: 259-267, 1994.
99. HU, X. F., T. J. MARTIN, D. R. BELL, M. DE LUISE, AND J. R. ZALCBERG. Combined use of cyclosporin A and verapamil in modulating multidrug resistance in human leukemia cell lines. Cancer Res. 50: 2953-2957, 1990.
100. HYAFIL, F., C. VERGELY, P. DU VIGNAUD, AND T. GRAND PERRET. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 53: 4595-4602, 1993.
101. INABA, M., H. KOBAYASHI, Y. SAKURAI, AND R. K. JOHNSON. Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. Cancer Res. 39: 2200-2203, 1979.
102. IZQUIERDO, M. A., R. H. SHOEMAKER, M. J. FLENS, G. L. SCHEFFER, L. WU, T. R. PRATHER, AND R. J. SCHEPER. Overlapping phenotypes of multidrug resistance among panels of human cancer-cell lines. Int. J. Cancer 65: 230-237, 1996.
103. JAKOBY, M. G., D. F. COVEY, AND D. P. CISTOLA. Localization of tolbutamide binding sites on human serum albumin using titration calorimetry and heteronuclear 2-D NMR. Biochemistry 34: 8780-8787, 1995.
104. JOHNSON, R., M. CHITNIS, W. EMBREY, AND E. GREGORY. In vivo characteristics of resistance and cross-resistance of an adriamycin-resistant subline of P388 leukemia. Cancer Treat. Rep. 62: 1535-1547, 1978.
105. KAJIJI, S., F. TALBOT, K. GRIZZUTI, V. VAN DYKE PHILLIPS, M. AGRESTI, A. R. SAFA, AND P. GROS. Functional analysis of P-glycoprotein mutants identifies predicted transmembrane domain 11 as a putative drug binding site. Biochemistry 32: 4185-4194, 1993.
106. KANE, S. E., I. PASTAN, AND M. M. GOTTESMAN. Genetic basis of multidrug resistance of tumor cells. J. Bioenerg. Biomembr. 22: 593-618, 1990.
107. KAST, C., V. CANFIELD, R. LEVENSON, AND P. GROS. Membrane topology of P-glycoprotein as determined by epitope insertion: transmembrane organization of the N-terminal domain of mdr3. Biochemistry 34: 4402-4411, 1995.
108. KAYE, S. B. Clinical drug resistance: the role of factors other than P-glycoprotein. Am. J. Med. 99, Suppl: 40S-44S, 1995.
109. KEIZER, H. G., AND H. JOENJE. Increased cytosolic pH in multidrug-resistant human lung tumor cells: effect of verapamil. J. Natl. Cancer Inst. 81: 706-709, 1989.
110. KESSEL, D., AND C. WILBERDING. Mode of action of calcium antagonists which alter anthracycline resistance. Biochem. Pharmacol. 337: 1157-1160, 1984.
111. - and taurine efflux from HeLa cells by P-glycoprotein blockers correlates with calmodulin inhibition. J. Biol. Chem. 269: 29389-29394, 1994.
112. KLOPMAN, G., S. SRIVASTAVA, I. KOLOSSVARY, R. F. EPAND, N. AHMED, AND R. M. EPAND. Structure-activity study and design of multidrug-resistant reversal compounds by a computer automated structure evaluation methodology. Cancer Res. 52: 4121-4129, 1992.
113. KORONAKIS, E., C. HUGHES, I. MILISAV, AND V. KORONAKIS. Protein exporter function and in vitro ATPase activity are correlated in ABC-domain mutants of HlyB. Mol. Microbiol. 16: 87-96, 1995.
114. KORONAKIS, V., C. HUGHES, AND E. KORONAKIS. ATPase activity and ATP/ADP-induced conformational change in the soluble domain of the bacterial translocator HlyB. Mol. Microbiol. 8: 1163-1175, 1993.
115. KRISHNAMACHARY, N., AND M. S. CENTER. The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein. Cancer Res. 53: 3658-3661, 1993.
116. LAMPIDIS, T., C. CASTELLO, A. DEL GIGLIO, B. PRESSMAN, P. VIALLET, K. TREVORROW, G. VALET, H. TAPIERO, AND N. SAVARAJ. Relevance of the chemical charge of rhodamine dyes to multiple drug resistance. Biochem. Pharmacol. 38: 4267-4271, 1989.
117. LAN, L.-B., S. AYESH, E. LYUBIMOV, I. PASHINSKY, AND W. D. STEIN. Kinetic parameters for reversal of the multidrug pump as measured for drug accumulation and cell killing. Cancer Chemother. Pharmacol. 38: 181-190, 1996.
118. LANKELMA, J., H. S. MULDER, F. VAN MOURIK, H. W. WONG FONG SANG, R. KRAAYENHOF, AND R. VAN GRONDELLE. Cellular daunomycin fluorescence in multidrug resistant 2780 AD cells and its relation to cellular drug localisation. Biochim. Biophys. Acta 1093: 147-152, 1991.
119. LANKELMA, J., E. SPOELSTRA, H. DEKKER, AND H. BROXTERMAN. Evidence for daunomycin efflux from multidrug-resistant 2780AD human ovarian carcinoma cells against a concentration gradient. Biochim. Biophys. Acta 1055: 217-222, 1990.
120. LAVIE, E., AND G. BLAUER. Circular dichroism and hydrodynamic measurements of ternary protein-two ligand systems: serum albumin-bilirubin-drug or alcohol. Arch. Biochem. Biophys. 193: 191-203, 1979.
121. LEE, J.-S., K. PAULL, M. ALVAREZ, C. HOSE, A. MONKS, M. GREVER, A. T. BATES, AND S. E. FOJO. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Mol. Pharmacol. 46: 627-638, 1994.
122. LEE, T., AND D. ROBERTS. Flux of teniposide (VM-26) across the plasma membrane of teniposide-resistant sublines of L1210 cells. Cancer Res. 44: 2986-2990, 1984.
123. LEE, W. P., C. L. LEE, AND H. C. LIN. Glutathione S-transferase and glutathione peroxidase are essential in the early stages of Adriamycin resistance before P-glycoprotein overexpression in HOB1 lymphoma cells. Cancer Chemother. Pharmacol. 38: 45-51, 1996.
124. LEHNERT, M., W. S. DALTON, D. ROE, S. EMERSON, AND S. E. SALMON. Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in a human myeloma cell line model. Blood 77: 348-354, 1991.
125. LEIGHTON, J. C., AND L. J. GOLDSTEIN. P-glycoprotein in adult solid tumors. Hematol. Oncol. Clin. N. Am. 9: 251-273, 1995.
126. LEU, B.-L., AND J.-D. HUANG. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother. Pharmacol. 35: 432-436, 1995.
127. LEYLAND-JONES, B., W. DALTON, G. A. FISHER, AND B. I. SIKIC. Reversal of multidrug resistance to cancer chemotherapy. Cancer 72: 3484-3488, 1993.
128. LIEB, W. R., AND W. D. STEIN. Non-Stokesian nature of transverse diffusion within human red cell membranes. J. Membr. Biol. 92: 111-119, 1986.
129. LINCKE, C. R., A. BROEKS, I. THE, R. H. PLASTERK, AND P. BORST. The expression of two P-glycoprotein (pgp) genes in transgenic Caenorhabditis elegans is confined to intestinal cells. EMBO J. 12: 1615-1620, 1993.
130. LITMAN, T. Multifarmakon Resistens og pH Gradienter (MSc thesis). Copenhagen: Univ. of Copenhagen, 1991.
131. LITMAN, T., D. NIELSEN, T. SKOVSGAARD, AND K. BUKHAVE. Lipid composition of sensitive and multidrug resistant Ehrlich ascites tumor cells. Cell Pharmacol. 2: 9-14, 1995.
132. LOE, D. W., AND F. J. SHAROM. Interaction of multidrug-resistant Chinese hamster ovary cells with the peptide ionophore gramicidin D. Biochim. Biophys. Acta 1190: 72-84, 1994.
133. LOO, T. W., AND D. M. CLARKE. 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: 22957-22961, 1995.
134. LOO, T. W., AND D. M. CLARKE. Membrane topology of a cysteine-less mutant of human P-glycoprotein. J. Biol. Chem. 270: 843-848, 1995.
135. LOO, T. W., AND D. M. CLARKE. Mutations to amino acids located in predicted transmembrane segment 6 (TM6) modulate the activity and substrate specificity of human P-glycoprotein. Biochemistry 33: 14049-14057, 1994.
136. LOO, T. W., AND D. M. CLARKE. Rapid purification of human P-glycoprotein mutants expressed transiently in HEK 293 cells by Nickel-chelate chromotography and characterization of their drug-stimulated activities. J. Biol. Chem. 270: 21449-21452, 1995.
137. LOO, T. W., AND D. M. CLARKE. Reconstitution of drug-stimulated ATPase activity following co-expression of each half of human P-glycoprotein as separate polypeptides. J. Biol. Chem. 269: 7750-7755, 1994.
138. - currents in NIH/3T3 cells. Am. J. Physiol. 267 (Cell Physiol. 36): C650-C658, 1994.
139. LUM, B. L., G. A. FISHER, N. A. BROPHY, A. M. YAHANDA, K. M. ADLER, S. KAUBISCH, J. HALSEY, AND B. I. SIKIC. Clinical trials of modulation of multidrug resistance: pharmacokinetic and pharmacodynamic considerations. Cancer 72: 3502-3514, 1993.
140. LUM, B. L., AND M. GOSLAND. MDR expression in normal tissues. Hematol. Oncol. Clin. N. Am. 9: 319-336, 1995.
141. 3 exchange in Chinese hamster ovary cells. Biochemistry 33: 7239-7249, 1994.
142. LYUBIMOV, E., L.-B. LAN, I. PASHINSKY, S. AYESH, AND W. D. STEIN. Saturation reversal of the multidrug pump using many reversers in low-dose combinations. Anticancer Drugs 6: 727-735, 1995.
143. MA, Y. Z., AND E. W. TAYLOR. Kinetic mechanism of myofibril ATPase. Biophys. J. 66: 1542-1553, 1994.
144. MARIE, J.-P. P-glycoprotein in adult hematological malignancies. Hematol. Oncol. Clin. N. Am. 9: 239-249, 1995.
145. MARQUARDT, D., AND M. S. CENTER. Drug transport mechanisms in HL60 cells isolated for resistance to Adriamycin: evidence for nuclear drug accumulation and redistribution in resistant cells. Cancer Res. 52: 3157-3163, 1992.
146. MAYER, L. D., M. B. BALLY, M. J. HOPE, AND P. R. CULLIS. Uptake of antineoplastic agents into large unilamellar vesicles in response to a membrane potential. Biochim. Biophys. Acta 816: 294-302, 1985.
147. MAYER, L. D., L. C. L. TAI, M. B. BALLY, G. N. MITILENES, R. S. GINSBERG, AND P. R. CULLIS. Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients. Biochim. Biophys. Acta 1025: 143-151, 1990.
148. McGRATH, T., D. MARQUARDT, AND M. S. CENTER. Multiple mechanisms of adriamycin resistance in the human leukemia cell line CCRF-CEM. Biochem. Pharmacol. 38: 497-501, 1989.
149. MILLER, R. L., R. M. BUKOWSKI, G. T. BUDD, J. PURVIS, J. K. WEICK, K. SHEPARD, K. K. MIDHA, AND R. GANAPATHI. Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial. J. Clin. Oncol. 6: 880-888, 1988.
150. MILROY, R. A randomised clinical study of verapamil in addition to combination chemotherapy in small cell lung cancer. Br. J. Cancer 68: 813-818, 1993.
151. MOLINARI, A., M. CIANFRIGLIA, S. MESCHINI, A. CALCABRINI, AND G. ARANCIA. P-glycoprotein expression in the Golgi apparatus of multidrug-resistant cells. Int. J. Cancer 59: 789-795, 1994.
152. MORIYAMA, Y., T. MANABE, T. YOSHIMORI, Y. TASHIRO, AND M. FUTAI. ATP-dependent uptake of anti-neoplastic agents by acidic organelles. J. Biochem. 115: 213-218, 1994.
153. MOTZER, R. J., P. LYN, P. FISCHER, P. LIANES, R. L. NGO, C. CORDON CARDO, AND J. P. O'BRIEN. Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma. J. Clin. Oncol. 13: 1958-1965, 1995.
154. MULDER, H. S., J. LANKELMA, H. DEKKER, H. J. BROXTERMAN, AND H. M. PINEDO. Daunorubicin efflux against a concentration gradient in non-P-glycoprotein multidrug-resistant lung-cancer cells. Int. J. Cancer 59: 275-281, 1994.
155. MULDER, H. S., R. VAN GRONDELLE, H. V. WESTERHOFF, AND J. LANKELMA. A plasma membrane "vacuum cleaner" for daunorubicin in non-P-glycoprotein multidrug-resistant SW-1573 human non-small cell lung carcinoma cells. A study using fluorescence resonance energy transfer. Eur. J. Biochem. 218: 871-882, 1993.
156. MULLER, C., G. LAURENT, AND V. LING. P-glycoprotein stability is affected by serum deprivation and high cell density in multi-drug resistant cells. J. Cell. Physiol. 163: 538-544, 1995.
157. MULLER, M. R., K. LENNARTZ, M. R. NOWROUSIAN, R. DUX, T. TSURUO, M. F. RAJEWSKY, AND S. SEEBER. Improved flow-cytometric detection of low P-glycoprotein expression in leukaemic blasts by histogram subtraction analysis. Cytometry 15: 64-72, 1994.
158. MURREN, J. R., H. J. DURIVAGE, A. C. BUZAID, M. REISS, S. D. FLYNN, D. CARTER, AND W. N. HAIT. Trifluoperazine as a modulator of multidrug resistance in refractory breast cancer. Cancer Chemother. Pharmacol. 38: 65-70, 1996.
159. NIELSEN, D. L. Daunorubicin Resistant Ehrlich Acites Tumor Cells: Resistance, P-glycoprotein Expression, Steady State Accumulation, and Reversal (PhD thesis). Copenhagen: Univ. of Copenhagen, 1994.
160. NIELSEN, D., C. MAARE, AND T. SKOVSGAARD. Influx of daunorubicin in multidrug resistant Ehrlich ascites tumor cells: correlation to expression of P-glycoprotein and efflux. Influence of verapamil. Biochem. Pharmacol. 50: 443-450, 1995.
161. NIELSEN, D., C. MAARE, AND T. SKOVSGAARD. Kinetics of daunorubicin transport in Ehrlich ascites tumor cells with different expression of P-glycoprotein. Biochem. Pharmacol. 47: 2125-2135, 1994.
162. NOGAE, I., K. KOHNO, J. KIKUCHI, M. KUWANO, S.-I. AKIYAMA, A. KIUE, K.-I. SUZUKI, Y. YOSHIDA, M. M. CORNWELL, I. PASTAN, AND M. M. GOTTESMAN. Analysis of structural features of dihydropyridine analogs needed to reverse multidrug resistance and to inhibit photoaffinity labeling of P-glycoprotein. Biochem. Pharmacol. 38: 519-527, 1989.
163. OHNISHI, T., I. TAMAI, K. SAKANAKA, A. SAKATA, T. YAMASHIMA, J. YAMASHITA, AND A. TSUJI. In vivo and in vitro evidence for ATP-dependency of P-glycoprotein-mediated efflux of doxorubicin at the blood-brain barrier. Biochem. Pharmacol. 49: 1541-1544, 1995.
164. OUDE ELFERINK, R. P., R. OTTENHOFF, M. VAN WIJLAND, J. J. SMIT, A. H. SCHINKEL, AND A. K. GROEN. Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse. J. Clin. Invest. 95: 31-38, 1995.
165. PEARCE, H. L., A. R. SAFA, N. J. BACH, M. A. WINTER, M. C. CIRTAIN, AND W. T. BECK. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proc. Natl. Acad. Sci. USA 86: 5128-5132, 1989.
166. PEDERSEN, P. L., AND E. CARAFOLI. Ion motive ATPases. Trends Biochem. Sci. 12: 186-189, 1987.
167. PEREIRA, E., M. N. BORREL, M. FIALLO, AND A. GARNIER-SUILLEROT. Non-competitive inhibition of P-glycoprotein-associated efflux of THP-adriamycin by verapamil in living K562 leukemia cells. Biochim. Biophys. Acta 1225: 209-216, 1994.
168. PEREIRA, E., AND A. GARNIER-SUILLEROT. Correlation between the short-term measurements of drug accumulation in living cells and the long-term growth inhibition. Biochem. Pharmacol. 47: 1851-1857, 1994.
169. PINEDO, H. M., AND G. GIACCONE. P-glycoprotein - a marker of cancer-cell behavior (Editorial). N. Engl. J. Med. 333: 1417-1419, 1995.
170. PIWNICA-WORMS, D., M. L. CHIU, M. BUDDING, J. F. KRONAUGE, R. A. KRAMER, AND J. M. CROOP. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. Cancer Res. 53: 977-984, 1993.
171. PIWNICA-WORMS, D., V. V. RAO, J. F. KRONAUGE, AND J. M. CROOP. Characterisation of multidrug resistance P-glycoprotein transport function with an organotechnetium cation. Biochemistry 34: 12210-12220, 1995.
172. PRAET, M., F. DEFRISE-QUERTAIN, AND J. M. RUYSSCHAERT. Comparison of adriamycin and derivatives uptake into large unilamellar vesicles in response to membrane potential. Biochim. Biophys. Acta 1148: 342-350, 1993.
173. PRESANT, C. A., P. S. KENNEDY, C. WISEMAN, K. GALA, A. BOUZAGLOU, M. WYRES, AND V. NAESSIG. Verapamil reversal of clinical doxorubicin resistance in human cancer. A Wilshire Oncology Medical Group pilot phase I-II study. Am. J. Clin. Oncol. 9: 355-357, 1986.
174. RADERER, M., AND W. SCHEITHAUER. Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer 72: 3553-3563, 1993.
175. RAMU, A., D. GLAUBIGER, AND Z. FUKS. Reversal of acquired resistance to doxorubicin in P388 murine leukemia cells by tamoxifen and other triparanol analogues. Cancer Res. 44: 4392-4395, 1984.
176. RAMU, A., H. B. POLLARD, AND L. M. ROSARIO. Doxorubicin resistance in P388 leukemia: evidence for reduced drug influx. Int. J. Cancer 44: 539-547, 1989.
177. RAMU, A., AND N. RAMU. Reversal of multidrug resistance by phenothiazines and structurally related compounds. Cancer Chemother. Pharmacol. 30: 165-173, 1992.
178. RAO, U. S., AND G. A. SCARBOROUGH. Direct demonstration of high affinity interactions of immunosuppressant drugs with the drug binding site of the human P-glycoprotein. Mol. Pharmacol. 45: 773-776, 1994.
179. RAO, V. V., M. L. CHIU, J. F. KRONAUGE, AND D. PIWNICAWORMS. Expression of recombinant human multidrug resistance P-glycoprotein in insect cells confers decreased accumulation of technetium-99m-sestamibi. J. Nucl. Med. 35: 510-515, 1994.
180. RAVIV, Y., H. B. POLLARD, E. P. BRUGGEMANN, I. PASTAN, AND M. M. GOTTESMAN. Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells. J. Biol. Chem. 265: 3975-3980, 1990.
181. ROEPE, P. D. The role of the MDR protein in altered drug translocation across tumor cell membranes. Biochim. Biophys. Acta 1241: 385-406, 1995.
182. i homeostasis in multidrug-resistant (MDR) cells: further characterization of a series of MDR cell lines expressing different levels of P-glycoprotein. Biochemistry 32: 11042-11056, 1993.
183. RUETZ, S., AND P. GROS. Functional expression of P-glycoprotein in secretory vesicles. J. Biol. Chem. 269: 12277-12284, 1994.
184. RUETZ, S., M. RAYMOND, AND P. GROS. Functional expression of P-glycoprotein encoded by the mouse mdr3 gene in yeast cells. Proc. Natl. Acad. Sci. USA 90: 11588-11592, 1993.
185. SACHS, F. Ion channels as mechanical transducers. In: Cell Shape: Determinants, Regulation, and Regulatory Role, edited by W. D. Stein and F. Bronner. New York: Academic, 1989, p. 63.
186. SAEKI, T., K. UEDA, Y. TANIGAWARA, R. HORI, AND T. KOMANO. Human P-glycoprotein transports cyclosporin A and FK506. J. Biol. Chem. 268: 6077-6080, 1993.
187. SAEKI, T., K. UEDA, Y. TANIGAWARA, R. HORI, AND T. KOMANO. P-glycoprotein-mediated transcellular transport of MDR-reversing agents. FEBS Lett. 324: 99-102, 1993.
188. SAFA, A. R., R. K. STERN, K. CHOI, M. AGRESTI, I. TAMAI, N. D. MEHTA, AND I. B. RONINSON. Molecular basis of preferential resistance to colchicine in multidrug-resistant human cells conferred by Gly-185 - Val-185 substitution in P-glycoprotein. Proc. Natl. Acad. Sci. USA 87: 7225-7229, 1990.
189. SAMUELS, B. L., R. MICK, N. J. VOGELZANG, S. F. WILLIAMS, R. L. SCHILSKY, A. R. SAFA, S. M. O'BRIEN, AND M. J. RATAIN. Modulation of vinblastine resistance with cyclosporine: a phase I study. Clin. Pharmacol. Ther. 54: 421-429, 1993.
190. SAMUELS, B. L., AND M. J. RATAIN. Correspondence re: Xiu F. Hu et al., Combined use of cyclosporin A and verapamil in modulating multidrug resistance in human leukemia cell lines (Cancer Res. 50: 2953-2957, 1990). Cancer Res. 51: 1749-1750, 1991.
191. SARKADI, B., M. MULLER, L. HOMOLYA, Z. HOLLO, J. SEPRODI, U. A. GERMANN, M. M. GOTTESMAN, E. M. PRICE, AND R. C. BOUCHER. Interaction of bioactive hydrophobic peptides with the human multidrug transporter. FASEB J. 8: 766-770, 1994.
192. SARKADI, B., E. M. PRICE, R. C. BOUCHER, U. A. GERMANN, AND G. A. SCARBOROUGH. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J. Biol. Chem. 267: 4854-4858, 1992.
193. SCHEFFER, G. L., P. L. WIJNGAARD, M. J. FLENS, M. A. IZQUIERDO, M. L. SLOVAK, H. M. PINEDO, C. J. MEIJER, H. C. CLEVERS, AND R. J. SCHEPER. The drug resistance-related protein LRP is the human major vault protein. Nature Med. 1: 578-582, 1995.
194. SCHINKEL, A. H., J. J. M. SMIT, O. VAN TELLINGEN, J. H. BEIJNEN, E. WAGENAAR, L. VAN DEEMTER, C. A. A. M. MOL, M. A. VAN DER VALK, E. C. ROBANUS-MAADAG, H. P. J. TE RIELE, A. J. M. BERNS, AND P. BORST. 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: 491-502, 1994.
195. SCHUURHUIS, G. J., H. J. BROXTERMAN, A. CERVANTES, T. H. VAN HEIJNINGEN, J. H. DE LANGE, J. P. BAAK, H. M. PINEDO, AND J. LANKELMA. Quantitative determination of factors contributing to doxorubicin resistance in multidrug-resistant cells. J. Natl. Cancer Inst. 81: 1887-1892, 1989.
196. SCHUURHUIS, G. J., H. J. BROXTERMAN, J. H. DE LANGE, H. M. PINEDO, T. H. VAN HEIJNINGEN, C. M. KUIPER, G. L. SCHEFFER, R. J. SCHEPER, C. K. VAN KALKEN, J. P. BAAK, AND J. LANKELMA. Early multidrug resistance, defined by changes in intracellular doxorubicin distribution, independent of P-glycoprotein. Br. J. Cancer 64: 857-861, 1991.
197. SCHUURHUIS, G. J., T. H. VAN HEIJNINGEN, A. CERVANTES, H. M. PINEDO, J. H. DE LANGE, H. G. KEIZER, H. J. BROXTERMAN, J. P. BAAK, AND J. LANKELMA. Changes in subcellular doxorubicin distribution and cellular accumulation alone can largely account for doxorubicin resistance in SW-1573 lung cancer and MCF-7 breast cancer multidrug resistant tumour cells. Br. J. Cancer 68: 898-908, 1993.
198. SEGEL, I. W. Enzyme Kinetics. New York: Wiley, 1975.
199. SEHESTED, M., D. SIMPSON, T. SKOVSGAARD, AND P. B. JENSEN. Freeze-fracture study of plasma membranes in wild type and daunorubicin-resistant Ehrlich ascites tumor and P388 leukemia cells. Virchows Arch. B Cell Pathol. 56: 327-335, 1989.
200. SEHESTED, M., T. SKOVSGAARD, M. L. JENNINGS, E. J. F. DEMANT, E. FRICHE, AND N. BINDSLEV. Transport of the multidrug resistance modulators verapamil and azidopine in wild type and daunorubicin resistant Ehrlich ascites tumor cells. Br. J. Cancer 62: 37-41, 1990.
201. SEHESTED, M., T. SKOVSGAARD, B. VAN DEURS, AND H. WINTHER-NIELSEN. Increase in nonspecific adsorptive endocytosis in anthracycline- and vinca alkaloid-resistant Ehrlich ascites tumor cell lines. J. Natl. Cancer Inst. 78: 171-179, 1987.
202. SHALINSKY, D. R., A. P. JEKUNEN, J. E. ALCARAZ, R. D. CHRISTEN, S. KIM, S. KHATIBI, AND S. B. HOWELL. Regulation of initial vinblastine influx by P-glycoprotein. Br. J. Cancer 67: 30-36, 1993.
203. SHAPIRO, A. B., AND V. LING. ATPase activity of purified and reconstituted P-glycoprotein from Chinese hamster ovary cells. J. Biol. Chem. 269: 3745-3754, 1994.
204. SHAPIRO, A. B., AND V. LING. Reconstitution of drug transport by purified P-glycoprotein. J. Biol. Chem. 270: 16167-16175, 1995.
205. SHARMA, R. C., S. INOUE, J. ROITELMAN, R. T. SCHIMKE, AND R. D. SIMONI. Peptide transport by the multidrug resistance pump. J. Biol. Chem. 267: 5731-5734, 1992.
206. SHAROM, F. J., G. DIDIODATO, X. YU, AND K. J. D. ASHBOURNE. Interaction of the P-glycoprotein multidrug transporter with peptides and ionophores. J. Biol. Chem. 270: 10334-10341, 1995.
207. SHAROM, F. J., X. YU, J. W. K. CHU, AND C. A. DOIGE. Characterization of the ATPase activity of P-glycoprotein from multidrug resistant Chinese hamster ovary cells. Biochem. J. 308: 381-390, 1995.
208. SHAROM, F. J., X. YU, AND C. A. DOIGE. Functional reconstitution of drug transport and ATPase activity in proteoliposomes containing partially purified P-glycoprotein. J. Biol. Chem. 268: 24197-24202, 1993.
209. SHIBUKAWA, A., Y. YOSHIMOTO, T. OHARA, AND T. NAKAGAWA. High-performance capillary electrophoresis/frontal analysis for the study of protein binding of a basic drug. J. Pharmacol. Sci. 83: 616-619, 1994.
210. SIROTNAK, F. M., C.-H. YANG, L. S. MINES, E. ORIBE, AND J. L. BIEDLER. Markedly altered membrane transport and intracellular binding of vincristine in multidrug-resistant Chinese hamster cells selected for resistance to Vinca alkaloids. J. Cell. Physiol. 126: 266-274, 1986.
211. SKOVSGAARD, T. Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cells. Cancer Res. 38: 4722-4727, 1978.
212. SKOVSGAARD, T. Mechanisms of resistance to daunorubicin in Ehrlich ascites tumor cells. Cancer Res. 38: 1785-1791, 1978.
213. SKOVSGAARD, T. Circumvention of resistance to daunorubicin by N-acetyldaunorubicin in Ehlich ascites tumor. Cancer Res. 40: 1077-1083, 1980.
214. SKOVSGAARD, T. Transport and multi-drug resistance. Indications of a changed pH-gradient across the membrane. In: Drug Resistance Mechanisms and Reversal, edited by E. Mihich. Rome: Libbey, 1990, p. 209.
215. SLOVAK, M., G. HOELTGE, W. DALTON, AND J. TRENT. Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. Cancer Res. 48: 2793-2797, 1988.
216. SMETS, L. A. Programmed cell death (apoptosis) and response to anti-cancer drugs. Anticancer Drugs 5: 3-9, 1994.
217. SMIT, J. J., A. H. SCHINKEL, R. P. OUDE ELFERINK, A. K. GROEN, E. WAGENAAR, L. VAN DEEMTER, C. A. MOL, R. OTTENHOFF, N. M. VAN DER LUGT, M. A. VAN ROON, M. A. VAN DER VALK, G. J. A. OFFERHAUS, A. J. M. BERNS, AND P. BORST. Homozygous disruption of the murine mdr2 p-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75: 451-462, 1993.
218. SNEDECOR, G. W., AND W. G. COCHRAN. Statistical Methods. Ames: Iowa State University Press, 1967.
219. SOUDON, J., M. BERLION, C. LUCAS, P. HADDA, J. P. BIZZARI, AND F. CALVO. In vitro activity of S 9788 on a multidrug-resistant leukemic cell line and on normal hematopoietic cells: reversal of multidrug resistance by sera from phase 1-treated patients. Cancer Chemother. Pharmacol. 36: 195-203, 1995.
220. SOUES, S., F. LAVAL, AND J. Y. CHARCOSSET. Mechanisms of resistance to combinations of vincristine, etoposide and doxorubicin in Chinese hamster ovary cells. Br. J. Cancer 71: 489-497, 1995.
221. SPEEG, K. V. J., C. DELEON, AND W. L. McGUIRE. Uptake of the noncytotoxic transport probe procainamide in the Chinese hamster ovary model of multidrug resistance. Cancer Res. 52: 3539-3546, 1992.
222. 222a. SPEELMANS, G., R. W. STAFFHORST, B. DE KRUIJFF, AND F. A. DE WOLF. Transport studies of doxorubicin in model membranes indicate a difference in passive diffusion across and binding at the outer and inner leaflets of the plasma membrane. Biochemistry 33: 13761-13768, 1994.
223. SPOELSTRA, E., H. V. WESTERHOFF, H. DEKKER, AND J. LANKELMA. Kinetics of daunorubicin transport by P-glycoprotein of intact cancer cells. Eur. J. Biochem. 207: 567-579, 1992.
224. SPOELSTRA, E. C., H. V. WESTERHOFF, H. M. PINEDO, H. DEKKER, AND J. LANKELMA. The multidrug-resistance-reverser verapamil interferes with cellular P-glycoprotein-mediated pumping of daunorubicin as a non-competing substrate. Eur. J. Biochem. 221: 363-373, 1994.
225. SRIDHAR, K. S., A. KRISHAN, T. S. A. SAMY, R. C. DUNCAN, A. SAUERTEIG, G. V. McPHEE, M. E. AUGUSTE, AND P. W. BENEDETTO. Phase I and pharmacokinetics studies of prochlorperazine 2-H I. V. Infusion as a doxorubicin-efflux blocker. Cancer Chemother. Pharmacol. 34: 377-384, 1994.
226. STEIN, W. D. Transport and Diffusion Across Cell Membranes. Orlando, FL: Academic, 1986.
227. STEIN, W. D. Channels, Carriers, and Pumps: an Introduction to Membrane Transport. San Diego, CA: Academic, 1990.
228. STEIN, W. D., C. CARDARELLI, I. PASTAN, AND M. M. GOTTESMAN. Kinetic evidence suggesting that the multidrug transporter differentially handles influx and efflux of its substrates. Mol. Pharmacol. 45: 763-772, 1994.
229. TAMAI, I., AND A. R. SAFA. Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. J. Biol. Chem. 266: 16796-16800, 1991.
230. TANG-WAI, D. F., S. KAJIJI, F. DICAPUA, D. DE GRAAF, I. B. RONINSON, AND P. GROS. Human (MDR1) and mouse (mdr1, mdr3) P-glycoproteins can be distinguished by their respective drug resistance profiles and sensitivity to modulators. Biochemistry 34: 32-39, 1995
231. THIEBAUT, F., T. TSURUO, H. HAMADA, M. M. GOTTESMAN, I. PASTAN, AND M. C. WILLINGHAM. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 84: 7735-7738, 1987.
232. TIDEFELT, U., G. JULIUSSON, A. ELMHORN ROSENBORG, C. PETERSON, AND C. PAUL. Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A. Eur. J. Haematol. 52: 276-282, 1994.
233. TODD, A., R. MEHLHORN, AND R. MACEY. Amine and carboxylate spin probe permeability in red cells. J. Membr. Biol. 109: 41-52, 1989.
234. TOFFOLI, G., F. SIMONE, G. CORONA, M. RASCCHACK, B. CAPPELLETO, M. GIGANTE, AND M. BOIOCCHI. Structure-activity relationships of verapamil analogs and reversal of multidrug resistance. Biochem. Pharmacol. 50: 1245-1255, 1995.
235. TOMINAGA, M., T. TOMINAGA, A. MIWA, AND Y. OKADA. Volume-sensitive chloride channel activity does not depend on endogenous P-glycoprotein. J. Biol. Chem. 270: 27887-27893, 1995.
236. TREZISE, A. E., P. R. ROMANO, D. R. GILL, S. C. HYDE, F. V. SEPULVEDA, M. BUCHWALD, AND C. F. HIGGINS. The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression. EMBO J. 11: 4291-4303, 1992.
237. TSURUO, T., H. IIDA, S. TSUKAGOSHI, AND Y. SAKURAI. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res. 41: 1967-1972, 1981.
238. TSURUO, T., H. IIDA, M. YAMASHIRO, S. TSUKAGOSHI, AND Y. SAKURAI. Enhancement of vincristine- and adriamycin-induced cytotoxicity by verapamil in P388 leukemia and its sublines resistant to vincristine and adriamycin. Biochem. Pharmacol. 31: 3138-3140, 1982.
239. TWENTYMAN, P. R., T. RHODES, AND S. RAYNER. A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and MRP-associated multidrug resistance phenotypes. Eur. J. Cancer 30A: 1360-1369, 1994.
240. UEDA, K., N. OKAMURA, M. HIRAI, Y. TANIGAWARA, T. SAEKI, N. HOKA, T. KOMANO, AND R. HORI. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J. Biol. Chem. 267: 24248-24252, 1992.
241. URBATSCH, I. L., M. K. AL-SHAWI, AND A. E. SENIOR. Characterization of the ATPase activity of purified Chinese hamster P-glycoprotein. Biochemistry 33: 7069-7076, 1994.
242. URBATSCH, I. L., B. SANKARAN, S. BHAGAT, AND A. E. SENIOR. Both P-glycoprotein nucleotide-binding sites are catalytically active. J. Biol. Chem. 270: 26956-26961, 1995.
243. URBATSCH, I. L., B. SANKARAN, J. WEBER, AND A. E. SENIOR. P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J. Biol. Chem. 270: 19383-19390, 1995.
244. URBATSCH, I. L., AND A. E. SENIOR. Effects of lipids on ATPase activity of purified Chinese hamster P-glycoprotein. Arch. Biochem. Biophys. 316: 135-140, 1995.
245. VALVERDE, M. A., M. DIAZ, F. SEPULVEDA, D. GILL, S. HYDE, AND C. HIGGINS. Volume-regulated chloride channel associated with the human multidrug resistance P-glycoprotein. Nature Lond. 355: 830-833, 1992.
246. VASEY, P. A., D. BISSETT, M. STROLIN-BENEDETTI, I. POGGESI, M. BREDA, L. ADAMS, P. WILSON, M. A. PACCIARINI, S. B. KAYE, AND J. CASSIDY. Phase 1 clinical and pharmacokinetic study of 3′-deamino-3′(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762). Cancer Res. 55: 2090-2096, 1995.
247. VICKERS, S. E., AND J. R. WARR. Changes in the nature of P-glycoprotein gene transcripts during the development of multidrug resistance in CHO cells. Cell Biol. Int. 19: 35-41, 1995.
248. WADKINS, R. M., AND P. J. HOUGHTON. The role of drug-lipid interactions in the biological activity of modulators of multi-drug resistance. Biochim. Biophys. Acta 1153: 225-236, 1993.
249. WALTER, A., AND J. GUTKNECHT. Permeability of small nonelectrolytes through lipid bilayer membranes. J. Membr. Biol. 90: 207-217, 1986.
250. WANG, Q., H. YANG, D. W. MILLER, AND W. F. ELMQUIST. Effect of the P-glycoprotein inhibitor, cyclosporin A, on the distribution of rhodamine-123 to the brain: an in vivo microdialysis study in freely moving rats. Biochem. Biophys. Res. Commun. 211: 719-726, 1995.
251. WATANABE, T., M. INABA, AND Y. SUGIYAMA. Saturable process involved in active efflux of vincristine as a mechanism of multidrug resistance in P388 leukemia cells. Pharm. Res. 6: 690-696, 1989.
252. WEAVER, J. L., G. SZABO, J. S. PINE, M. M. GOTTESMAN, S. GOLDENBERG, AND A. ASZALOS. The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multi-drug transporter. Int. J. Cancer 54: 456-461, 1993.
253. WEI, L. Y., AND P. D. ROEPE. Low external pH and osmotic shock increase the expression of human MDR protein. Biochemistry 33: 7229-7238, 1994.
254. WEI, L. Y., M. J. STUTTS, M. M. HOFFMAN, AND P. D. ROEPE. Overexpression of the cystic fibrosis transmembrane conductance regulator in NIH 3T3 cells lowers membrane potential and intracellular pH and confers a multidrug resistance phenotype. Biophys. J. 69: 883-895, 1995.
255. WELKER, E., K. SZABO, Z. HOLLO, M. MULLER, B. SARKADI, AND A. VARADI. Drug-stimulated ATPase activity of a deletion mutant of the human multidrug-resistance protein (MDR). Biochem. Biophys. Res. Commun. 216: 602-609, 1995.
256. WILLINGHAM, M. C., M. M. CORNWELL, C. O. CARDARELLI, M. M. GOTTESMAN, AND I. PASTAN. Single cell analysis of daunomycin uptake and efflux in multidrug-resistant and -sensitive KB cells: effects of verapamil and other drugs. Cancer Res. 46: 5941-5946, 1986.
257. XIANG, T.-X., AND B. D. ANDERSON. The relationship between permeant size and permeability in lipid bilayer membranes. J. Membr. Biol. 140: 57-68, 1994.
258. + channel current associated with multidrug resistance in human leukemia cells. Cancer Res. 47: 3736-3741, 1987.
259. ZAMORA, J. M., H. L. PEARCE, AND W. T. BECK. Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Mol. Pharmacol. 33: 454-562, 1988.
260. ZEUTHEN, T., AND W. D. STEIN. Cotransport of salt and water in membrane proteins: membrane proteins as osmotic engines. J. Membr. Biol. 137: 179-195, 1994.