Functional expression and localization of P-glycoprotein in the central nervous system: Relevance to the pathogenesis and treatment of neurological disorders

Pharmaceutical Research

Volumn 21, Issue 8, 2004, Pages 1313-1330

  Lee, Gloria ^a   Bendayan, Reina ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

brain; neurological diseases; P glycoprotein; transporter

Indexed keywords

ANTINEOPLASTIC AGENT; ANTIRETROVIRUS AGENT; BIRICODAR; BREAST CANCER RESISTANCE PROTEIN; CALCIUM CHANNEL BLOCKING AGENT; CALMODULIN INHIBITOR; CEFOPERAZONE; CYCLOSPORIN A; DEXNIGULDIPINE; DEXVERAPAMIL; DOXORUBICIN; ELACRIDAR; ETOPOSIDE; GLUCOSE TRANSPORTER 1; GLUTAMATE TRANSPORTER; GLYCOPROTEIN P; IVERMECTIN; LY 336979; MULTIDRUG RESISTANCE PROTEIN; NUCLEOSIDE TRANSPORTER; OC 144093; ORGANIC ANION TRANSPORTER; ORGANIC CATION TRANSPORTER; PACLITAXEL; PROTEINASE INHIBITOR; QUININE; RIFAMPICIN; RITONAVIR; RYANODINE RECEPTOR; STEROID; TACROLIMUS; TARIQUIDAR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALSPODAR; VERAPAMIL; VINBLASTINE; VINCRISTINE;

ASTROCYTE; BINDING SITE; BLOOD BRAIN BARRIER; BRAIN TUMOR; CEREBROSPINAL FLUID; CEREBROVASCULAR DISEASE; CORRELATION ANALYSIS; CYTOKINE PRODUCTION; DEMENTIA; DRUG EFFECT; DRUG MECHANISM; DRUG PENETRATION; DRUG POTENCY; DRUG SOLUBILITY; DRUG TRANSPORT; ENDOCYTOSIS; ENZYME BINDING; EPILEPSY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY ASSOCIATED DEMENTIA; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROPHOBICITY; MAJOR HISTOCOMPATIBILITY COMPLEX; MEMBRANE PERMEABILITY; MICROENVIRONMENT; MICROGLIA; MOLECULAR MECHANICS; NERVE CELL; NONHUMAN; OLIGODENDROGLIA; PARENCHYMA; PARKINSON DISEASE; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STATISTICAL SIGNIFICANCE;

AIDS DEMENTIA COMPLEX; ALZHEIMER DISEASE; ANIMALS; BLOOD-BRAIN BARRIER; BRAIN; BRAIN NEOPLASMS; CENTRAL NERVOUS SYSTEM DISEASES; DRUG RESISTANCE, MULTIPLE; HUMANS; P-GLYCOPROTEIN; PARKINSON DISEASE;

EID: 4344561089     PISSN: 07248741     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:PHAM.0000036905.82914.8e     Document Type: Review

References (279)

1. E. K. Rowinsky, L. Smith, Y. M. Wang, P. Chaturvedi, M. Villalona, E. Campbell, C. Aylesworth, S. G. Eckhardt, L. Hammond, M. Kraynak, R. Drengler, J. Stephenson, M. W. Harding, and D. D. Von Hoff. Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agents that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP. J. Clin. Oncol. 16:2964-2976 (1998).
2. C. Wandel, R. B. Kim, S. Kajiji, P. Guengerich, G. R. Wilkinson, and A. J. Wood. P-glycoprotein and cytochrome P450 3A inhibtion: Dissociation of inhibitory potencies. Cancer Res. 59:3944-3948 (1999).
3. R. Krishna and L. D. Mayer. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur. J. Pharm. Sci. 11:265-283 (2000).
4. F. Hyafil, 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).
5. A. H. Dantzig, R. L. Shepard, K. L. Law, L. Tabas, S. Pratt, J. S. Gillespie, S. N. Binkley, M. T. Kuhfeld, J. J. Starling, and S. A. Wrighton. Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J. Pharmacol. Exp. Ther. 290:854-862 (1999).
6. M. J. Newman, J. C. Rodarte, K. D. Benbatoul, S. J. Romano, C. Zhang, S. Krane, E. J. Moran, R. T. Uyeda, R. Dixon, E. S. Guns, and L. D. Mayer. Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res. 60:2964-2972 (2000).
7. M. Maliepaard, M. A. van Gastelen, A. Tohgo, F. H. Hausheer, R. C. van Waardenburg, L. A. de Jong, D. Pluim, J. H. Beijnen, and J. H. Schellens. Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin. Cancer Res. 7:935-941 (2001).
8. O. B. Paulson. Blood-brain barrier, brain metabolism and cerebral blood flow. Eur. Neuropsychopharmacol. 12:495-501 (2002).
9. M. W. Brightman. Morphology of blood-brain barrier. Exp. Eye Res. 25:1-25 (1977).
10. N. J. Abbott. Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat. 200:629-638 (2002).
11. A. G. De Boer, I. C. van der Sandt, and P. J. Gaillard. The role of drug transporters at the blood-brain barrier. Annu. Rev. Pharmacol. Toxicol. 43:629-656 (2003).
12. A. N. Butt, H. C. Jones, and J. N. Abbott. Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J. Physiol. 429:47-62 (1990).
13. K. Kacem, P. Lacombe, J. Seylaz, and G. Bonvento. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23:1-10 (1998).
14. P. Seeman and H. Kalant. Drug solubility, absorption, and movement across body membranes. In H. Kalant and W. H. Roschlau (eds.). Principles of Medical Pharmacology, 5th edition, B.C. Decker Inc, Burlington, Ontario, Canada, 1989, pp. 14-20.
15. M. H. Abraham and J. A. Platts. Physichochemical factors that influence brain uptake. In D. J. Begley, M. W. Bradbury, and J. Kreuter (eds.), The Blood Brain Barrier and Drug Delivery to the CNS, Marcel Dekker, New York. 2000, pp. 9-32.
16. M. Simionescu, A. Gafencu, and F. Antohe. Transcytosis of plasma macromolecules in endothelial cells: a cell biological survey. Microsc. Res. Tech. 57:269-288 (2002).
17. N. Simionescu, F. Lupu, and M. Simionescu. Rings of membrane sterols surround the opening of vesicles and fenestrae, in capillary endothelium. J. Cell Biol. 97:1592-1600 (1983).
18. R. G. Anderson, B. A. Kamen, K. G. Rothberg, and S. W. Lacey. Potocytosis: sequestration and transport of small molecules by caveolae. Science 255:410-411 (1992).
19. R. Montesano, J. Roth, A. Robert, and L. Orci. Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins. Nature 296:651-653 (1982).
20. D. Tran, J. L. Carpentier, F. Sawano, P. Gorden, and L. Orci. Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway. Proc. Natl. Acad. Sci. USA 84:7957-7961 (1987).
21. M. P. Lisanti, P. E. Scherer, Z. L. Tang, and M. Sargiacomo. Caveolae, caveolin and caveolin-rich membrane domains: a signaling hypothesis. Trends Cell Biol. 4:231-235 (1994).
22. W. M. Pardridge and R. J. Boado. Molecular cloning and regulation of gene expression of blood-brain barrier glucose transporter. In W. M. Pardridge (ed.), The Blood-Brain Barrier. Cellular and Molecular Biology. Raven Press, New York, 1993, pp. 395-440.
23. G. Lee, S. Dallas, M. Hong, and R. Bendayan. Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations. Pharmacol. Rev. 53:569-596 (2001).
24. J. F. Ghersi-Egea, B. Leninger-Muller, G. Suleman, G. Siest, and A. Minn. Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. J. Neurochem. 62:1089-1096 (1994).
25. M. B. Segal. The choroid plexuses and the barriers between the blood and the cerebrospinal fluid. Cell. Mol. Neurobiol. 20:183-196 (2000).
26. J. F. Ghersi-Egea and N. Strazielle. Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexus. Microscopy Res. Tech. 52:83-88 (2001).
27. M. R. Del Bigio. The ependyma: a protective barrier between brain and cerebrospinal fluid. Glia 14:1-13 (1995).
28. 22Na in the cerebrospinal fluid and the brain. J Physiol 209:131-153 (1970).
29. C. E. Johanson, S. M. Sweeney, J. T. Parmelee, and M. H. Epstein. Co-transport of sodium and chloride by the adult mammalian choroid plexus. Am. J. Physiol. 258:C211-C216 (1990).
30. A. Schmitt, E. Asan, K. P. Lesch, and P. Kugler. A splice variant of glutamate transporter GLT1/EAAT2 expressed in neurons: cloning and localization in rat nervous system. Neuroscience 109:45-61 (2002).
31. Y. Tochino and L. S. Schanker. Active transport of quaternary ammonium compounds by the choroid plexus in vitro. Am. J. Physiol. 208:666-673 (1965).
32. Y. Tochino and L. S. Schanker. Transport of serotonin and norepinephrine by the rabbit choroid plexus in vitro. Biochem. Pharmacol. 14:1557-1566 (1965).
33. M. T. Whittico, Y. A. Gang, and K. M. Giacomini. Cimetidine transport in isolated brush border membrane vesicles from bovine choroid plexus. J. Pharmacol. Exp. Ther. 255:615-623 (1990).
34. L. Li, T. K. Lee, and P. J. Meier. N. and Ballatori. Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatpl, the hepatic sinusoidal organic solute transporter. J. Biol. Chem. 273:16184-16191 (1998).
35. X. Wu, M.M. Gutierrez, and K.M. Giacomini. Further characterization of the sodium-dependent nucleoside transporter (N3) in choroid plexus from rabbit. Biochim. Biophys. Acta 1191:190-196 (1994).
36. X. Wu, G. Yuan, C. M. Brett, A. C. Hui, and K. M. Giacomini. Sodium-dependent nucleoside transport in choroid plexus from rabbit. Evidence for a single transporter for purine and pyrimidine nucleosides. J. Biol. Chem. 267:8813-8818 (1992).
37. V. V. Rao, J. L. Dahlheimer, M. E. Bardgett, A. Z. Snyder, R. A. Finch, A. C. Sartorelli, and D. Piwnica-Worms. Choroid plexus epithelial expression of MDR1 P-glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal fluid drug permeability barrier. Proc. Natl. Acad. Sci. USA 96:3900-3905 (1999).
38. B. Volk, U. Hettmannsperger, T. Papp, Z. Amelizad, F. Oesch, and R. Knoth. Mapping of phenytoin-inducible cytochrome P450 immunoreactivity in the mouse central nervous system. Neuroscience 42:215-235 (1991).
39. M. Lindvall, J. E. Hardebo, and C. Owman. Barrier mechanisms for neurotransmitter monamines in the choroid plexus. Acta Physiol. Scand. 108:215-221 (1980).
40. I. Tayarani, I. Cloez, M. Clement, and J. M. Bourre. Antioxidant enzymes and related trace elements in aging brain capillaries and choroid plexus. J. Neurochem. 53:817-824 (1989).
41. G. Perea and A. Araque. Communication between astrocytes and neurons: a complex language. J Physiol 96:199-207 (2002).
42. W. E. Van Heyningen. The fixation of tetanus toxin, strychnine, serotonin and other substances by ganglioside. J. Gen. Microbiol. 31:375-387 (1963).
43. M. C. Raff, E. R. Abeny, J. Cohen, R. Lindsay, and M. Noble. Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides and growth characteristics. J. Neurosci. 3:1289-1300 (1983).
44. P. E. Duffy. Astrocytes: Normal, Reactive and Neoplastic, Raven Press, New York, 1983.
45. C. G. Tedeschi. Neuropathology: Methods and Diagnosis, Little, Brown and Co., Boston, 1970.
46. W. Walz. Controversy surrounding the existence of discrete functional classes of astrocytes in adult gray matter. Glia 31:95-103 (2000).
47. Y. Dong Y. and E. N. Benveniste. Immune functions of astrocytes. Glia 36:180-190 (2001).
48. P. G. Haydon. Neuroglia networks: neurons and glia talk to eachother. Curr. Biol. 10:R712-R714 (2000).
49. E. N. Benveniste. Cytokine actions in the central nervous system. Cytokine Growth Factor Rev. 9:259-275 (1998).
50. M. Aschner. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicol. Lett. 102-103:283-287 (1998).
51. H. Wolburg and W. Risau. Neuroglia. In B. R. Ransom and H. Kettenmann (eds.), Formation of the Blood-Brain Barrier. Oxford University Press, New York, 1995, pp. 763-776.
52. U. V. Malipiero, K. Frei, and A. Fontana. Production of hemopoietic colony stimulating factors by astrocytes. J. Immunol. 144:3816-3821 (1990).
53. B. Pearce, J. Albrecht, C. Morrow, and S. Murphy. Astrocyte glutamate receptor activation promotes inositol phospholipid turnover and calcium flux. Neurosci. Lett. 72:335-340 (1986).
54. B. I. Kanner. Glutamate transporters from brain. A novel neurotransmitter transport family. FEBS Lett. 325:95-99 (1993).
55. P. Rakic. Principles of neural cell migration. Experientia 46:882-891 (1990).
56. S. Yu and W. G. Ding. The 45 kDa form of glucose transporter 1 (GLUT1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain. Brain Res. 797:65-72 (1998).
57. M. Domercq, M. V. Sanchez-Gomez, P. Areso, and C. Matute. Expression of glutamate transporters in rat optic nerve oligodendrocytes. Eur. J. Neurosci. 11:2226-2236 (1999).
58. U. V. Berger, H. Tsukaguchi, and M. A. Hediger. Distribution of mRNA for the facilitated urea transporter UT3 in the rat nervous system. Anat. Embryol. 197:405-414 (1998).
59. E. Hosli and L. Hosli. Autoradiographic studies on the uptake of adenosine and on binding of adenosine analogues in neurons and astrocytes of cultured rat cerebellum and spinal cord. Neuroscience 24:621-628 (1988).
60. J. G. Gu, A. Nath, and J. D. Geiger. Characterization of inhibitor-sensitive and resistant adenosine transporters in cultured human fetal astrocytes. J. Neurochem. 67:972-977 (1996).
61. C. J. Sinclair, C. G. LaRiviere, J. D. Young, C. E. Cass, S. A. Baldwin, and F. E. Parkinson. Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions. J. Neurochem. 75:1528-1538 (2000).
62. P. B. Simpson, L. A. Holtzclaw, D. B. Langley, and J. T. Russell. Characterization of ryanodine receptors in oligodendrocytes, type 2 astrocytes, and O-2A progenitors. J. Neurosci. Res. 52:468-482 (1998).
63. W. Zhang, J. Mojsilovic-Petrovic, M. F. Andrade, H. Zhang, M. Ball, and D. B. Stanimirovic. Expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J. 17:2085-2087 (2003).
64. W. M. Pardridge. Drug delivery to the brain. J. Cereb. Blood Flow Metab. 17:713-731 (1997).
65. X. Decleves, A. Regina, J. L. Laplanche, F. Roux, B. Boval, J. M. Launay, and J. M. Scherrmann. Functional expression of P-glycoprotein and multidrug resistance-associated protein (Mrp1) in primary cultures of rat astrocytes. J. Neurosci. Res. 60:594-601 (2000).
66. P. Ronaldson, M. Bendayan, D. Gingras, M. Piquette-Miller, R. Bendayan. Cellular localization and functional expression of P-glycoprotein in rat astrocyte cultures. J. Neurochem. 89:788-800 (2004).
67. P. Ronaldson, G. Lee, S. Dallas, and R. Bendayan. Involvement of P-glycoprotein in the transport of saquinavir and indinavir in rat brain microvessel endothelial and microglia cell lines. Pharm. Res. 21:811-818 (2004).
68. S. E. Pfeiffer, A. E. Warrington, and R. Bansal. The oligodendrocyte and its many cellular processes. Trends Cell Biol. 3:191-197 (1993).
69. R. Wilson and P. J. Brophy. Role for the oligodendrocyte cytoskeleton in myelination. J. Neurosci. Res. 22:439-448 (1989).
70. K. Ainger, D. Avossa, F. Morgan, S. J. Hill, C. Barry, E. Barbarese, and J. H. Carson. Transport and localization of exogenous myelin basic protein mRNA microinjected into oligodendrocytes. J. Cell Biol. 123:431-441 (1993).
71. P. J. Brophy, G. L. Bocaccio, and D. R. Colman. The distribution of myelin basic protein mRNAs within myelinating oligodendrocytes. Trends Neurosci. 16:515-521 (1993).
72. B. D. Trapp, G. J. Kidd, P. Hauer, E. Mulrenin, C. A. Haney, and S. B. Andrews. Polarization of myelinating Schwann cell surface membranes: role of microtubules and the trans-Golgi network. J. Neurosci. 15:1797-1807 (1995).
73. Y. Tanaka, K. Yamada, C. J. Zhou, N. Ban, S. Shioda, and N. Inagaki. Temporal and spatial profiles of ABCA2-expressing oligodendrocytes in the developing rat brain. J. Comp. Neurol. 455:353-367 (2003).
74. F. Maher. Immunolocalization of GLUT1 and GLUT3 glucose transporters in primary cultured neurons and glia. J. Neurosci. Res. 42:459-469 (1995).
75. O. Braissant, T. Gotoh, M. Loup, M. Mori, and C. Bachmann. Differential expression of the cationic amino acid transporter 2(B) in the adult rat brain. Brain Res. Mol. Brain Res. 91:189-195 (2001).
76. K. Gipson and A. Bordey. Analysis of the K+ current profile of mature rat oligodendrocytes in situ. J. Membr. Biol. 189:201-212 (2002).
77. J. Hirrlinger, J. Konig, and R. Dringen. Expression of mRNAs of multidrug resistance proteins (Mrps) in cultured rat astrocytes, oligodendrocytes, microglial cells and neurones. J. Neurochem. 82:716-719 (2002).
78. P. E. Knapp, O. S. Itkis, and M. Mata. Neuronal interaction determines the expression of the alpha-1 isoform of Na/K-ATPase in oligodendrocytes. Brain Res. Dev. Brain Res. 125:89-97 (2000).
79. P. T. Massa, S. Saha, C. Wu, and K. W. Jarosinski. Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes. Glia 29:376-385 (2000).
80. N. Chattopadhyay, C. P. Ye, T. Yamaguchi, O. Kifor, P. M. Vassilev, R. Nishimura, and E. M. Brown. Extracellular calcium-sensing receptor in rat oligodendrocytes: expression and potential role in regulation of cellular proliferation and an outward K+ channel. Glia 24:449-458 (1998).
81. L. J. Lawson, V. H. Perry, P. Dri, and S. Gordon. Heterogeneity in the distribution and morphology of microglia in the normal, adult mouse brain. Neuroscience 39:151-170 (1990).
82. P. Del Rio Hortega. Microglia. In. W. Penfield (ed.), Cytology and Cellular Pathology of the Nervous System, Hoeber, New York, 1932, pp. 481-584.
83. E. J. Davis, T. D. Foster, and W. E. Thomas. Cellular forms and functions of brain microglia. Brain Res. Bull. 34:73-78 (1994).
84. W. J. Streit and G. W. Kreutzberg. Lectin binding by resting and reactive microglia. J. Neurocytol. 16:249-260 (1987).
85. J. A. Glenn, P. L. Booth, and W. E. Thomas. Pinocytotic activity in ramified microglia. Neurosci. Lett. 123:27-31 (1991).
86. P. A. Ransom and W. E. Thomas. Pinocytosis as a select marker of ramified microglia in vivo and in vitro. J. Histochem. Cytochem. 39:853-858 (1991).
87. S. A. Ward, P. A. Ransom, P. L. Booth, and W. E. Thomas. Characterization of ramified microglia in tissue culture-pinocytosis and motility. J. Neurosci. Res. 29:13-28 (1991).
88. M. B. Graeber, W. J. Streit, and G. W. Kreutzberg. The microglial cytoskeleton: Vimentin is localized within activated cells in situ. J. Neurocytol. 17:573-580 (1988).
89. M. B. Graeber, W. J. Streit, and G. W. Kreutzberg. Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells. J. Neurosci. Res. 21:18-24 (1988).
90. W. J. Streit, M. B. Graeber, and G. W. Kreutzberg. Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. J. Neuroimmunol. 21:117-123 (1989).
91. H. Akiyama, T. Arai, H. Kondo, E. Tanno, C. Haga, and K. Ikeda. Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Dis Assoc Discord 1:S47-S53 (2000).
92. J. B. Brierley and A. W. Brown. The origin of lipid phagocytes in the central nervous system. I. The intrinsic microglia. J. Comp. Neurol. 211:397-406 (1982).
93. W. J. Streit and G. W. Kreutzberg. Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin. J. Comp. Neurol. 268:248-263 (1988).
94. R. B. Banati, J. Gehrmann, P. Schubert, and G. W. Kreutzberg. Cytotoxicity of microglia. Glia 7:111-118 (1993).
95. G. W. Kreutzberg. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19:312-318 (1996).
96. S. Chabot, G. Williams, and V. W. Yong. Microglia production of TNF-alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferon beta-1b. J. Clin. Invest. 100:604-612 (1997).
97. K. Todd and R. F. Butterworth. Mechanisms of selective neuronal cell death due to thiamine deficiency. Ann. N. Y. Acad. Sci. 893:404-411 (1999).
98. M. Walton, B. Connor, P. Lawlor, D. Young, E. Sirimanne, P. Gluckman, G. Cole, and M. Dragunow. Neuronal death and survival in two models of hypoxic-ischemic brain damage. Brain Res. Brain Res. Rev. 29:137-168 (1999).
99. H. Xiong, Y. C. Zeng, T. Lewis, J. Zheng, Y. Persidsky, and H. E. Gendelman. HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1 associated dementia. J. Neurovirol. 6:S14-S23 (2000).
100. C. Frelin, P. Vigne, T. Jean, P. Barby, and M. Lazdunski. The role of the Na+/H+ antiport in cardiac cells, skeletal muscle cells, neuronal cells, and glial cells. In S. Grinstein (ed.), Na+/H+ Exchange, CRC Press LLC, Boca Raton, 1988, pp. 155-166.
101. R. Klee, U. Heinemann, and C. Eder. Voltage-gated proton currents in microglia of distinct morphology and functional state. Neuroscience 91:1415-1424 (1999).
102. M. Noda, H. Nakanishi, J. Nabekura, and N. Akaike. Ampakainate subtypes of glutamate receptor in rat cerebral microglia. J. Neurosci. 20:251-258 (2000).
103. M. Hong, L. Schlichter, and R. Bendayan. A Na+ dependent nucleoside transporter in microglia. J. Pharmacol. Exp. Ther. 292:366-374 (2000).
104. M. Hong, L. Schlichter, and R. Bendayan. A novel zidovudine uptake system in microglia. J. Pharmacol. Exp. Ther. 296:141-149 (2001).
105. G. Lee, L. Schlichter, M. Bendayan, and R. Bendayan. Functional expression of P-glycoprotein in rat brain microglia. J. Pharmacol Exp. Ther. 299:204-212 (2001).
106. S. Dallas, X. Zhu, S. Baruchel, L. Schlichter, and R. Bendayan. Functional expression of the multidrug resistance protein 1 in microglia. J. Pharmacol. Exp. Ther. 307:282-290 (2003).
107. S. Dallas, L. Schlichter, and R. Bendayan. Multidrug resistance proteins (MRP)4 and MRP5-mediated efflux of 9-(2-phosphonylmethoxyethyl) adenine by microglia. J. Pharmacol. Exp. Ther. 309:1221-1229 (2004).
108. P. F. Juranka, R. L. Zastawny, and V. Ling. P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J. 3:2583-2592 (1989).
109. K. Ueda, M. M. Cornwell, M. M. Gottesman, I. Pastan, I. B. Roninson, V. Ling, and J. R. Riordan. The mdr1 gene responsible for multidrug resistance codes for P-glycoprotein. Biochim. Biophys. Res. Commun. 141:956-962 (1986).
110. J. A. Endicott and V. Ling. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 58:137-171 (1989).
111. J. E. Chin, R. Soffir, K. E. Noonan, and K. Choi, and I. B. Roninson. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol. Cell. Biol. 9:3808-3820 (1989).
112. A. Devault A. and P. Gros. Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities. Mol. Cell. Biol. 10:1652-1663 (1990).
113. P. Gros, M. Raymond, J. Bell, and D. Housmann. Cloning and characterization of a second member of the mouse mdr gene family. Mol. Cell. Biol. 8:2770-2778 (1988).
114. K. Ueda, C. Cardarelli, M. M. Gottesman, and I. Pastan. Expression of a full length cDNA for the human mdr1 gene confers resistance to colchicine, doxorubicin and vinblastine. Proc. Natl. Acad. Sci. USA 84:3004-3008 (1987).
115. P. Gros, Y. Ben Neriah, J. M. Croop, and D. E. Housman. Isolation and expression of a cDNA (mdr) that confers multidrug resistance. Nature 323:728-731 (1986).
116. J. J. Smit, A. H. Schinkel, R. Oude Elferink, A. K. Groen, E. Wagenaar, L. Van Deemter, C. A. Mol, R. Ottenhoff, N. M. Van der Lugt, M. Can Room, M. A. Van der Valk, G. J. Offerhaus, A. J. 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).
117. C. J. Chen, 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).
118. W. T. Beck and M. C. Cirtain. Continued expression of vinca alkaloid resistance by CCRF-CEM cells after treatment with tunicamycin or pronase. Cancer Res. 209:184-189 (1982).
119. H. Hamada, K. I. Hagiwara, T. Nakajima, and T. Tsuruo. Phosphorylation of the 170,000 to 180,000 glycoprotein specific to multidrug resistant tumor cells: effects of verapamil, trifluoperazine and phorbol esters. Cancer Res. 47:2860-2865 (1987).
120. F. Thiebaut, T. Tsuruo, H. Hamada, M. M. Gottesman, I. Pastan, and M. C. Willingham. Cellular localization of the multidrug resistance gene product in normal human tissues. Proc. Natl. Acad. Sci. USA 84:7735-7738 (1987).
121. R. J. Arceci, J. M. Croop, S. B. Horwitz, and D. Housman. The gene encoding multidrug resistance is induced and expressed at high levels during pregnancy in the secretory epithelium of the uterus. Proc. Natl. Acad. Sci. USA 85:4350-4354 (1988).
122. P. M. Chaudhary and I. B. Roninson. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66:85-95 (1991).
123. D. Drach, S. Zhao, J. Drach, R. Mahadevia, C. Gattringer, H. Huber, and M. Andreeff. Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype. Blood 80:2451-2458 (1992).
124. W. T. Klimecki, B. W. Futscher, T. M. Grogan, and W. S. Dalton. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 83:2451-2458 (1994).
125. M. M. Gottesman and I. Pastan. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62:385-427 (1993).
126. C. F. Higgins and M. M. Gottesman. Is the multidrug transporter a flippase? Trends Biochem. Sci. 17:18-21 (1992).
127. F. J. Sharom. The P-glycoprotein efflux pump: how does it transport drugs? J. Membr. Biol. 160:161-175 (1997).
128. Y. Romsicki and F. J. Sharom. Phospholipid flippase activity of the reconstituted P-glycoprotein multidrug transporter. Biochemistry 40:6937-6947 (2001).
129. G. A. Fisher, B. L. Lum, J. Hausdorff, and B. I. Sikic. Pharmacological considerations in the modulation of multidrug resistance. Eur. J. Cancer 32A:1082-1088 (1996).
130. T. Saeki, K. Ueda, Y. Tanigawara, R. Hori, and T. Komano. Human P-glycoprotein transports cyclosporin A and FK506. J. Biol. Chem. 268:6077-6080 (1993).
131. Y. Tanigawara, N. Okamura, M. Hirai, M. Yasuhara, K. Ueda, N. Kioka, T. Komano, and R. Hori. Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLCPK). J. Pharm. Exp. Ther. 263:840-845 (1992).
132. E. G. Schuetz, W. T. Beck, and J. D. Schuetz. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately upregulate these proteins in human colon carcinoma cells. Mol. Pharmacol. 49:311-318 (1996).
133. C. L. Lee, M. M. Gottesman, C. O. Cardarelli, M. Ramachandra, K. T. Jeang, S. V. Ambudkar, I. Pastan, and S. Dey. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 37:3594-3601 (1998).
134. A. H. Schinkel, J. J. Smit, O. van Tellingen, J. G. Beijnen, E. Wagenaar, L. van Deemter, C. A. Mol, M. A. van der Valk, E. C. Robanus Maandag, H. P. te Riele, A. J. Berns, and P. Borst. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitive deficiency to drugs. Cell 77:491-502 (1994).
135. S. M. Witherspoon, D. L. Emerson, B. M. Kerr, T. L. Lloyd, W. S. Dalton, and P. S. Wissel. Flow cytometric assay of modulation of P-glycoprotein function in whole blood by the multidrug resistance inhibitor GG918. Clin. Cancer Res. 2:7-12 (1996).
136. A. Cayre, F. Cachin, J. Maublant, D. Mestas, V. Feillel, J. P. Ferriere, F. Kwiaktowski, S. Chevillard, F. Finat-Duclos, P. Verrelle, and F. Penault-Llorca. Single static view 99mTc-sestamibi scintimammography predicts response to neoadjuvant chemotherapy and is related to MDR expression. Int. J. Oncol. 20:1049-1055 (2002).
137. O. Fardel and V. Lecureur. and A. Guillouzo A. The P-glycoprotein multidrug transporter. Gen. Pharmacol. 27:1283-1291 (1996).
138. J. M. Ford. Modulators of multidrug resistance. Preclinical studies. Hematol. Oncol. Clin. North Am. 9:337-361 (1995).
139. D. R. Ferry, H. Traunecker, and D. J. Kerr. Clinical trials of P-glycoprotein reversal in solid tumors. Eur. J. Cancer 32A:1070-1081 (1996).
140. H. Thomas and H. M. Coley. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting P-glycoprotein. Cancer Control 10:159-165 (2003).
141. M. Roe, A. Folkes, P. Ashworth, J. Brumwell, L. Chima, S. Hunjan, I. Pretswell, W. Dangerfield, H. Ryder, and P. Charlton. Reversal of P-glycoprotein-mediated multidrug resistance by novel anthranilamide derivatives. Bioorg. Med. Chem. Lett. 9:595-600 (1999).
142. L. Van Zuylen, K. Nooter, and A. Sparreboom. and J. Verweij. Development of multidrug-resistance convertors: sense or non-sense? Invest. New Drugs 18:205-220 (2000).
143. A. Tsuji, T. Terasaki, Y. Takabatake, Y. Tenda, I. Tamai, T. Yamashima, S. Moritani, T. Tsuruo, and J. Yamashita. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 51:1427-1437 (1992).
144. J. Greenwood. Characterization of a rat retinal endothelial cell culture and the expression of P-glycoprotein in brain and retinal endothelium in vitro. J. Neuroimmunol. 39:123-132 (1992).
145. E. J. Hegmann, H. C. Bauer, and R. S. Kerbel. Expression and functional activity of P-glycoprotein in cultured cerebral capillary endothelial cells. Cancer Res. 52:6969-6975 (1992).
146. L. Jette, J. F. Pouliot, G. F. Murphy, and R. Beliveau. Isoform I (mdr3) is the major form of P-glycoprotein expressed in mouse brain capillaries. Evidence for cross-reactivity of antibody C219 with an unrelated protein. Biochem. J. 305:761-766 (1995).
147. D. Lechardeur, V. Phung-Ba, P. Wils, and D. Scherman. Detection of the multidrug resistance of P-glycoprotein in healthy tissues: the example of the blood-brain barrier. Ann. Biol. Clin. 54:31-36 (1996).
148. D. Lechardeur and D. Scherman. Functional expression of the P-glycoprotein mdr in primary cultures of bovine cerebral capillary endothelial cells. Cell Biol. Toxicol. 11:283-293 (1995).
149. D. J. Begley, D. Lechardeur, Z. D. Chen, C. Rollinson, M. Bardoul, F. Roux, D. Scherman, and N. J. Abbott. Functional expression of P-glycoprotein in an immortalized cell line of rat brain endothelial cells, RBE4. J. Neurochem. 67:988-995 (1996).
150. J. M. Rose, S. L. Peckham, J. L. Scism, and K. L. Audus. Evaluation of the role of P-glycoprotein in ivermectin uptake by cultures of bovine brain microvessel endothelial cells. Neurochem. Res. 23:203-209 (1998).
151. S. Seetharaman, M. A. Barrand, L. Maskell, and R. J. Scheper. Multidrug resistance-related transport proteins in isolated human brain microvessels and in cells cultured from these isolates. J. Neurochem. 70:1151-1159 (1998).
152. A. Regina, A. Koman, M. Piciotti, and B. El Hafny. M.S. Center, P.O. Bergmann, P.O. Couraud, and F. Roux. Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J. Neurochem. 71:705-715 (1998).
153. A. Regina, I. A. Romero, J. Greenwood, P. Adamson, J. M. Bourre, P. O. Couraud, and F. Roux. Dexamethasone regulation of P-glycoprotein activity in an immortalized rat brain endothelial cell line, GPNT. J. Neurochem. 73:1954-1963 (1999).
154. R. Bendayan, G. Lee, and M. Bendayan. Functional expression and localization of P-glycoprotein at the blood-brain barrier. Microsc. Res. Tech. 57:365-380 (2002).
155. M. Demeule, D. Shedid, E. Beaulieu, R. F. Del Maestro, A. Moghrabi, P. B. Ghosn, R. Moumdjian, F. Berthelet, and R. Beliveau. Expression of multidrug resistance P-glycoprotein (MDR1) in human brain tumors. Int. J. Cancer 93:62-66 (2001).
156. I. Sugawara, H. Hamada, T. Tsuruo, and S. Mori. Specialized localization of P-glycoprotein recognized by MRK16 monoclonal antibody in endothelial cells of the brain and the spinal cord. Jpn. J. Cancer Res. 81:727-730 (1990).
157. E. Beaulieu, M. Demeule, L. Ghitescu, and R. Beliveau. P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain. Biochem. J. 326:539-544 (1997).
158. L. Jette, B. Tetu, and R. Beliveau. High levels of P-glycoprotein detected in isolated brain capillaries. Biochim. Blophys. Acta 1150:147-154 (1993).
159. M. Demeule, A. Regina, J. Jodoin, A. Laplante, C. Dagenais, F. Berthelet, A. Moghrabi, and R. Beliveau. Drug transport to the brain: Key roles for the efflux pump P-glycoprotein in the blood-brain barrier. Vasc. Pharmacol. 38:339-348 (2002).
160. P. L. Golden and W. M. Pardridge. P-glycoprotein on atrocyte foot processes of unfixed isolated human brain capillaries. Brain Res. 819:143-146 (1999).
161. K. Toth, M. M. Vaughan, N. S. Peress, H. K. Slocum, and Y. M. Rustum. MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumors. Am. J. Pathol. 149:853-858 (1996).
162. T. Sawada, N. Kato, N. Sakayori, Y. Takekawa, and M. Kobayashi. Expression of the multidrug resistance P-glycoprotein (P-gp, MDR1) by endothelial cells of the neovasculature in central nervous system tumors. Brain Tumor Pathol. 16:23-27 (1999).
163. Y. Lavie, G. Fiucci, and M. Liscovitch. Up-regulation of caveolae and caveolar constituents in multidrug-resistant cancer cells. J. Biol. Chem. 273:32380-32383 (1998).
164. C. P. Yang, F. Galbiati, D. Volonte, S. B. Horwitz, and M. P. Lisanti. Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells. FEBS Lett. 439:368-372 (1998).
165. M. Demeule, J. Jodoin, D. Gingras, and R. Beliveau. P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries. FEBS Lett. 466:219-224 (2000).
166. J. E. Schnitzer, P. Oh, and E. Pinney. and J. Allard. Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J. Cell Biol. 127:1217-1232 (1994).
167. L. A. Doyle, W. Yang, L. V. Abruzzo, T. Krogmann, Y. Gao, A. K. Rishi, and D. D. Ross. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. USA 95:15665-15670 (1998).
168. H. C. Cooray, C. G. Blackmore, L. Maskell, and M. A. Barrand. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport 13:2059-2063 (2002).
169. T. Eisenblatter and H. J. Galla. A new multidrug resistance protein at the blood-brain barrier. Biochem. Biophys. Res. Commun. 293:1273-1278 (2002).
170. T. Eisenblatter, S. Huwel, and H. J. Galla. Characterization of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res. 971:221-231 (2003).
171. T. Litman, T. E. Druley, W. D. Stein, and S. E. Bates. From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell. Mol. Life Sci. 58:931-959 (2001).
172. P. Ballerini, P. D. Lorio, R. Ciccarelli, E. Nargi, L. D'Alimonte, U. Traversa, M. P. Rathbone, and F. Caciagli. Glial cells express multiple ATP binding cassette proteins which are involved in ATP release. Neuro report 13:1789-1792 (2002).
173. S. Spiegl-Kreinecker, J. Buchroithner, L. Elbling, E. Steiner, G. Wurm, A. Bodenteich, J. Fischer, M. Micksche, and W. Berger. Expression and functional activity of the ABC-transporter proteins P-glycoprotein and
174. C. A. Doige 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).
175. R. B. Kim, M. F. Fromm, C. Wandel, B. Leake, J. J. Alastair, D. M. Roden, and G. R. Wilkinson. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 101:289-294 (1998).
176. M. Bredel. Anticancer drug resistance in primary human brain tumors. Brain Res. Rev. 35:161-204 (2001).
177. T. Matsumoto, E. Tani, K. Kaba, N. Kochi, H. Shindo, Y. Yamamoto, and H. Sakamoto, and J. Furuyama. Amplification and expression of multidrug resistance gene in human glioma cell lines. J. Neurosurg. 72:96-101 (1990).
178. I. Becker, K. F. Becker, and R. Meyermann, and V. Hollt. The multidrug resistance gene MDR1 is expressed in human glial tumors. Acta Neuropathol. 82:516-519 (1991).
179. D. M. Tishler and C. Raffel. Development of multidrug resistance in a primitive neuroectodermal tumor cell line. J. Neurosurg. 76:502-506 (1992).
180. M. W. Nabors, C. A. Griffin, B. A. Zehnbauer, R. H. Hruban, P. C. Phillips, S. A. Grossman, H. Brem, and O. M. Colvin. Multidrug resistance gene (MDR1) expression in human brain tumors. J. Neurosurg. 75:941-946 (1991).
181. B. C. Liang. Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell lines. J. Neurooncol. 29:149-155 (1996).
182. M. Mousseau, C. Chauvin, M. F. Nissou, M. Chaffanet, D. Plantaz, B. Pasquier, R. Schaerer, and A. Benabid. A study of the expression of four chemoresistance-related genes in human primary and metastatic brain tumors. Eur. J. Cancer 29A:753-759 (1993).
183. P. von Bossanyi, S. Diete, M. Dietzmann, M. W. Kirches, and E. Kirches. Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy. Acta Neuropathol. 94:605-611 (1997).
184. K. Yokogami, H. Kawano, T. Moriyama, H. Uehara, T. Sameshima, T. Oku, T. Goya, S. Wakisaka, S. Nagamachi, S. Jinnouchi, and S. Tamura. Application of SPET using technetium-99m sestamibi in brain tumors and comparison with expression of the MDR1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99m Tc-sestamibi SPET? Eur. J. Nucl. Med. 25:401-409 (1998).
185. Y. Tanaka, Y. Abe, A. Tsugu, Y. Takamiya, A. Akatsuka, T. Tsuruo, H. Yamazaki, Y. Ueyama, O. Sato, N. Tamaoki, Y. Takamiya, A. Akatsuka, T. Tsuruo, H. Yamazaki, Y. Ueyama, O. Sato, and N. Tamaoki. Ultrastructural localization of P-glycoprotein on capillary endothelial cells in human gliomas. Virchows Arch. 425:133-138 (1994).
186. A. Korshunov, A. Golanv, R. Sycheva, I. Pronin, and L. Fadeeva. Prognostic value of the immunoexpression of chemoresistance-related proteins in cerebral glioblastomas: an analysis of 168 cases. Neuropathology 19:143-149 (1999).
187. J. M. Gallo, S. Li, P. Guo, and K. Reed, and J. Ma. The effect of P-glycoprotein on paclitaxel brain and brain tumor distribution in mice. Cancer Res. 63:5114-5117 (2003).
188. X. Decleves, A. Fajac, J. Lehmann-Che, M. Tardy, C. Mercier, I. Hurbain, J. L. Laplanche, J. F. Bernaudin, and J. M. Scherr mann. Molecular and functional MDR1-P-gp and MRPs expression in human glioblastoma multiforme cell lines. Int. J. Cancer 98:173-180 (2002).
189. F. Leweke, M. S. Damian, C. Schlindler, and W. Schachenmayr. Multidrug resistance in glioblastoma: chemosensitivity testing and immunohistochemical demonstration of P-glycoprotein. Pathol. Res. Pract. 194:149-155 (1998).
190. H. J. Schluesener and R. Meyermann. Spontaneous Multidrug transport in human glioma cells is regulated by transforming growth factors type beta. Acta Neuropathol. 81:641-648 (1991).
191. J. W. Henson, C. Cordon-Cardo, and J. B. Posner. P-glycoprotein expression in brain tumors. J. Neurooncology 14:37-43 (1992).
192. G. J. Dore, P. Correll, Y. Li, J. M. Kaldor, D. A. Cooper, and B. J. Brew. Changes to AIDs dementia complex in the era of highly active antiretroviral therapy. AIDS 13:1249-1253 (1999).
193. J. H. McArthur, O. A. Seines, L. P. Jacobson, B. R. Visscher, M. Concha, and A. Saah. Dementia in AIDS patients: incidence and risk factors. Neurology 43:2245-2252 (1993).
194. J. A. McArthur, N. Haughey, S. Gartner, K. Conant, C. Pardo, V. Nath, and N. Sacktor. Human immunodeficiency virus-associated dementia: an evolving disease. J. Neurovirol. 9:205-221 (2003).
195. V. Valcour, B. Shiramizu, C. Shikuma, P. Poff, M. Watters, J. Grove, O. Selnes, and N. Sacktor. Neurocognitive function among older compared to younger HIV-1 seropositive individuals. J. Neuro Virol. 8:69 (2002).
196. G. J. Dore, A. McDonald, Y. Li, J. M. Kaldor, and B. Brew. Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17:1539-1545 (2003).
197. B. Navia, B. D. Jordon, and R. W. Price. The AIDS dementia complex: I. Clinical features. Ann. Neurol. 19:517-524 (1986).
198. G. J. Nuovo. In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids and tumor necrosis factor-α RNA in the central nervous system. Am. J. Pathol. 144:659-666 (1994).
199. O. Bagasra, E. Lavi, L. Bobroski, K. Khalili, J. P. Pestaner, R. Tawadros, and R. J. Pomerantz. Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10:573-585 (1996).
200. L. G. Epstein and H. E. Gendelman. Human immunodeficiency virus type 1 infection of the nervous system: pathogenic mechanisms. Ann. Neurol. 33:429-436 (1993).
201. M. Kaul, G. A. Garden, and S. A. Lipton. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988-994 (2001).
202. D. M. Rausch, E. A. Murray, and L. E. Eiden. The SIV-infected rhesus monkey model for HIV-associated dementia and implications for neurological diseases. J. Leukocyte Biol. 65:466-474 (1999).
203. A. Nath. Pathobiology of human immunodeficiency virus dementia. Semin. Neurol. 19:113-127 (1999).
204. T. W. Chun, L. Stuyver, S. B. Mizell, L. A. Ehler, J. A. Mican, M. Baseler, A. L. Lloyd, M. A. Nowak, and A. S. Fauci. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl. Acad. Sci. USA 94:13193-13197 (1997).
205. S. G. Deeks, M. Smith, M. Holodniy, and J. O. Kahn. HIV-1 protease inhibitors. A review for clinicians. JAMA 277:145-153 (1997).
206. J. Alsenz, H. Steffen, and R. Alex. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharm. Res. 15:423-428 (1998).
207. L. Profit, V. A. Eagling, and D. J. Back. Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS 13:1623-1627 (1999).
208. A. E. Kim, J. M. Dintaman, D. S. Waddell, and J. A. Silverman. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J. Pharmacol. Exp. Ther. 286:1439-1445 (1998).
209. C. B. Washington, H. R. Whiltshire, M. Man, T. Moy, S. R. Harris, E. Worth, P. Weigl, Z. Liang, D. Hall, L. Marriott, and T. F. Blaschke. The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats and in cultured cells. Drug Metab. Dispos. 28:1058-1062 (2000).
210. E. F. Choo, B. Leake, C. Wandel, H. Imamura, A. J. Wood, G. R. Wilkinson, and R. B. Kim. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab. Dispos. 28:655-660 (2002).
211. S. Gollapudi and S. Gupta. Human immunodeficiency virus I-induced expression of P-glycoprotein. Biochem. Biophys. Res. Commun. 171:1002-1007 (1990).
212. A. Andreana, S. Aggarwal, S. Gollapudi, D. Wien, T. Tsuruo, and S. Gupta. Abnormal expression of a 170-kilodalton P-glycoprotein encoded by MDR1 gene, a metabolically active efflux pump, in CD4+ and CD8+ T cells from patients with human immunodeficiency virus type 1 infection. AIDS Res. Hum. Retroviruses 12:1457-1462 (1996).
213. W. Malorni, M. B. Lucia, G. Rainaldi, R. Cauda, M. Cianfiglia, G. Donelli, and L. Ortona. Intracellular expression of P170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV infected patients. Haematologica 83:12-20 (1998).
214. E. R. Meaden, P. G. Hoggard, B. Maher, S. H. Khoo, and D. J. Back. Expression of P-glycoprotein and multidrug resistance-associated protein in healthy volunteers and HIV-infected patients. AIDS Res. Hum. Restroviruses 17:1329-1332 (2001).
215. C. Agrati, F. Poccia, S. Topino, P. Narciso, C. Selva, L. P. Pucillo, G. D'Offizi, G. Antonelli, F. Bellomi, O. Turriziani, and F. Bambacioni. P-glycoprotein expression by peripheral blood mononuclear cells from human immunodeficiency virus-infected patients is independent from response to highly active antiretroviral therapy. Clin. Diagnostic Lab. Immunol. 10:191-192 (2003).
216. M. D. Perloff, L. L. Von Moltke, J. E. Marchand, and D. J. Greenblatt. Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. J. Pharm. Sci. 90:1829-1837 (2001).
217. L. Huang, S. A. Wring, J. L. Woolley, K. R. Brouwer, C. Serabjit-Singh, and J. W. Polli. Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhihitors. Drug Metab. Dispos. 29:754-760 (2001).
218. E. R. Meaden, P. G. Hoggard, P. Newton, J. F. Tjia, D. Aldam, D. Cornforth, J. Llyod, I. Williams, D. J. Back, and S. H. Khoo. P-glycoprotein and MRP1 expression and reduced ritonavir and saquinavir accumulation in HIV-infected individuals. J. Antimicrob. Chemother. 50:583-588 (2002).
219. M. L. Dupuis, M. Flego, A. Molinari, and M. Cianfriglia. Saquinavir induces stable and functional expression of the multidrug transporter P-glycoprotein in human CD4 T-lymphoblastoid CEMrev cells. HIV Med. 4:338-345 (2003).
220. B. Chandler, L. Almond, J. Ford, A. Owen, P. Hoggard, S. Khoo, and D. Back. The effects of protease inhibitors and non-nucleoside reverse transcriptase inhibitors on P- glycoprotein expression in peripheral blood mononuclear cells in vitro. J. Acquir. Immune Defic. Syndr. 33:551-556 (2003).
221. N. A. Roberts. Drug-resistance patterns of saquinavir and other HIV protease inhibitors. AIDS 9:S27-S32 (1995).
222. P. Bossi, O. Legrand, A. M. Faussat, M. Legrand, F. Bricaire, J. P. Marie, H. Agut, B. Diquet, C. Katlama, J. M. Huraux, and V. Calvez. P-glycoprotein in blood CD4 cells of HIV-1 infected patients treated with protease inhibitors. HIV Med. 4:67-71 (2003).
223. K. Yusa, T. Oh-Hara, S. Tsukahara, W. Satoh, and T. Tsuruo. Cross-resistance to anti-HIV nucleoside analogs in multidrug-resistant human cells. Biochem. Biophys. Res. Commun. 169:986-990 (1990).
224. D. Mayers. Rational approaches to resistance: nucleoside analogues. AIDS 10:S9-13 (1996).
225. T. R. Browne and G. L. Holmes. Epilepsy. N. Engl. J. Med. 344:1145-1151 (2001).
226. National Institutes of Health. National Institutes of Health Consensus Conference: surgery for epilepsy. J. Am. Med. Assoc. 264:729-733 (1990).
227. J. W. Sander. Some aspects of prognosis in the epilepsies: a review. Epilepsia 34:1007-1016 (1993).
228. G. Regesta and P. Tanganelli. Clinical aspects and biological bases of drug resistant epilepsies. Epilepsy Res. 34:109-122 (1999).
229. D. M. Tishler, K. T. Weinberg, D. R. Hinton, N. Barbara, G. M. Annett, and C. Raffel. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 36:1-6 (1995).
230. S. M. Dombrowski, S. Y. Desai, M. Marroni, L. Cucullo, K. Goodrich, W. Bingaman, M. R. Mayberg, L. Bengez, and D. Janigro. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 42:1501-1506 (2001).
231. S. M. Sisodiya, J. Heffernan, and M. V. Aquier. Over-expression of P-glycoprotein in malformations of cortical development. Neuroreport 10:3437-3441 (1999).
232. S. M. Sisodiya, W. R. Lin, B. N. Harding, M. V. Squier, and M. Thom. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 125:22-31 (2002).
233. A. Lazarowski, G. Sevlever, A. Taratuto, M. Massaro, and A. Rabinowicz. Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr. Neurol. 21:731-734 (1999).
234. S. M. Sisodiya, W. R. Lin, M. V. Squier, and M. Thom. Multidrug resistance protein 1 in focal cortical dysplasia. Lancet 357:42-43 (2001).
235. E. Aronica, J. A. Gorter, H. Jansen, C. W. M. Van Veelen, P. C. Van Rijen, S. Leenstra, M. Ramkema, G. L. Scheffer, R. J. Scheper, and D. Troost. Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors. Neuroscience 118:417-429 (2003).
236. M. Rizzi, S. Caccia, G. Guiso, C. Richichi, J. A. Gorter, E. Aronica, M. Aliprandi, R. Bagnati, R. Fanelli, M. D'Incalci, R. Samanin, and A. Vezzani. Limbic seizures induce P-glycoprotein in rodent brain: functional implications for pharmaoresistance. J. Neurosci. 22:5833-5839 (2002).
237. W. Loscher and H. Potschka. Role of multidrug transporters in pharmacoresistance to antiepeileptic drugs. J. Pharmacol. Exp. Ther. 301:7-14 (2002).
238. H. Potschka and W. Loscher. In vivo evidence for P-glycoprotein mediated transport of phenytoin at the blood brain barrier of rats. Epilepsia 42:1231-1240 (2001).
239. H. Potschka, M. Fedrowitz, and W. Loscher. P-glycoprotein mediated efflux of Phenobarbital, lamotrigine, and felbamate at the blood brain barrier: evidence from microdialysis experiments in rats. Neurosci. Lett. 327:173-176 (2002).
240. A. Owen, M. Pirmohamed, J. N. Tettey, P. Morgan, D. Chadwick, and K. Park. Carbamazepine is not a substrate for P-glycoprotein. Br. J. Clin. Pharmacol. 51:345-349 (2001).
241. E. N. Benvenist, V. T. Nguyen, and G. M. O'Keefe. Immunological aspects of microglia: relevance to Alzheimer's disease. Neurochem. Int. 39:381-391 (2001).
242. D. J. Selkoe. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399:A23-A31 (1999).
243. D. Giulian. Neurogenetics '99. Microglia and the immune pathology of Alzheimer disease. Am. J. Hum. Genet. 65:13-18 (1999).
244. T. Uchihara, H. Akiyama, H. Kondo, and K. Ikeda. Activated microglial cells are colocalized with perivascular deposits of amyloid-β protein in Alzheimer's disease brain. Stroke 28:1948-1950 (1997).
245. J. L. Cummings, H. V. Vinters, G. M. Cole, and A. S. Khachaturian. Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology 51:S2-S17 (1998).
246. D. J. Selkoe. Towards a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid B-protein. Ann. N. Y. Acad. Sci. 924:17-25 (2000).
247. F. C. Lam, R. Liu, A. B. Shapiro, J. M. Renoir, F. J. Sharom, and P. B. Reiner. B-amyloid efflux mediated by P-glycoprotein. J. Neurochem. 76:1121-1128 (2001).
248. S. Vogelgesang, I. Cascorbi, E. Schroeder, J. Pahnke, H. K. Kroemer, W. Siegmund, C. Kunert-Keil, L. C. Walker, and R. W. Warzok. Deposition of Alzheimer's B-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Pharmacogenetics 12:535-541 (2002).
249. C. Haass, M. G. Schlossmacher, A. Y. Hung, C. Vigo-Pelfrey, A. Mellon, B. L. Ostaszewki,. I. Lieberburg, E. H. Koo, D. Schenk, D. B. Templow, and D. J. Selkoe. Amyloid-B peptide is produced by cultured cells during normal metabolism. Nature 359:322-325 (1992).
250. M. Shoji, T. E. Golde, J. Ghiso, T. T. Cheung, S. Estus, L. M. Shaffer, X. D. Cai, D. M. McKay, R. Tintner, B. Frangione and S. G. Younkin. Production of the Alzheimer amyloid-B protein by normal proteolytic processing. Science 258:126-129 (1992).
251. J. Busciglio, D. H. Gabuzda, P. Matsudaira, and B. A. Yankner. Generation of B-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc. Natl. Acad. Sci. USA 90:2092-2096 (1993).
252. J. M. Croop. Evolutionary relationships among ABC transporters. Methods Enzymol. 292:101-116 (1998).
253. S. V. Ambudkar, S. Dey, C. A. Hrycyna, M. Ramachandra, I. Pastan, and M. M. Gottesman. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39:361-398 (1999).
254. T. Yakushi, K. Masuda, S. I. Narita, and H. Tokuda. A new ABC transporter mediating the detachment of lipid-modified proteins from membranes. Nat. Cell Biol. 2:212-218 (2000).
255. D. J. Gruol, M. C. Zee, J. Trotter, and S. Bourgeois. Reversal of multidrug resistance by RU 486. Cancer Res. 54:3088-3091 (1994).
256. V. Marsaud, C. Mercier-Bodard, D. Fortin, S. Le Bihan, and J. M. Renoir. Dexamethasone and triamcinolone acetonide accumulation in mouse fibroblasts is differently modulated by the immunosuppressants cyclosporin A, FK506, rapamycin and their analogues, as well as by other P-glycoprotein ligands. J. Steroid Biochem. Mol. Biol. 66:11-25 (1998).
257. K. Bogman, A. K. Peyer, M. Torok, E. Kusters, and J. Drewe. HMG-CoA reductase inhibitors and P-glycoprotein modulation. Br. J. Pharmacol. 132:1183-1192 (2001).
258. G. J. Hooiveld, T. A. Vos, G. L. Scheffer, H. van Goor, H. Koning, V. Bloks, A. E. Loot, D. K. Meijer, P. L. Jansen, F. Kuipers, and M. Muller. 3-hydroxy-3-methylglutaryl-conenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats. Gastroenterology 117:678-687 (1999).
259. K. Fassbender, M. Simons, C. Bergmann, M. Stroick, D. Lutjohann, P. Keller, H. Runz, S. Kuhl, T. Bertsch, K. von Bergmann, M. Hennerici, K. Beyreuther, and T. Hartmann. Simvastatin strongly reduces levels of Alzheimer's disease B-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo. Proc. Natl. Acad. Sci. USA 98:5856-5861 (2001).
260. K. L. Davis, L. J. Thal, E. R. Gamzu, C. S. Davis, R. F. Woolson, S. I. Gracon, D. A. Drachman, L. S. Schneider, P. J. Whitehouse, and T. M. Hoover. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group. N. Engl. J. Med. 327:1253-1259 (1992).
261. S. L. Rogers, M. R. Farlow, R. S. Doody, R. Mohs, and L. T. Friedhoff. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology 50:136-145 (1998).
262. M. Rosler, R. Anand, A. Cicin-Sain, S. Gauthier, Y. Agid, P. Dal-Bianco, H. B. Stahelin, R. Hartman, and M. Gharabawi. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: International randomized controlled trial. BMJ 318:633-638 (1999).
263. M. A. Raskind, E. R. Peskind, T. Wessel, and W. Yuan. Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54:2261-2268 (2000).
264. P. B. Molinoff. AB modulation: the next generation of AD therapeutics. Neurobiol. Aging 21:S136 (2000).
265. D. B. Schenk, R. Barbour, W. Dunn, G. Gordon, H. Grajeda, T. Guido, K. Hu, J. Huang, K. Johnson-Wood, K. Khan, D. Kholodenko, M. Lee, Z. Liao, I. Lieberburg, R. Motter, L. Mutter, F. Soriano, G. Shopp, N. Vasquez, C. Vandevert, S. Walker, M. Wogulis, T. Yednock, D. Games, and P. Seubert. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173-177 (1999).
266. D. B. Schenk, P. Seubert, and I. Liberburg. and J. Wallace. Beta-peptide immunization: a possible new treatment for Alzheimer disease. Arch. Neurol. 57:934-936 (2000).
267. Y. Ben-Shlomo and K. Sieradzan. Idiopathic parkinson's disease: epidemiology, diagnosis and management. Br. J. Gen. Pract. 45:261-268 (1995).
268. T. Kitada, S. Asakawa, N. Hattori, H. Matsumine, Y. Yamamura, S. Minoshima, M. Yokochi, Y. Mizuno, and N. Shimizu. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605-608 (1998).
269. D. Maimone, R. Dominici, and L. M. Grimaldi. Pharmacogenomics of neurodegenerative diseases. Eur. J. Pharmacol. 413:11-29 (2001).
270. J. W. Langston, P. Ballard, J. W. Tetrud, and I. Irwin. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979-980 (1983).
271. W. Koller, B. Vetere-Overfield, C. Gray, C. Alexander, T. Chin, J. Dolezal, R. Hassanein, and C. Tanner. Environmental risk factors in Parkinson's disease. Neurology 40:1218-1221 (1990).
272. K. M. Semchuk, E. J. Love, and R. G. Lee. Parkinson's disease and exposure to agricultural work and pesticide chemicals. Neurology 42:1328-1335 (1992).
273. R. Betarbet, T. B. Sherer, G. MacKenzie, M. Garcia-Osuna, A. V. Panov, and J. T. Greenamyre. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3:1301-1306 (2000).
274. P. M. Christensen, P. C. Gotzsche, and K. Brosen. The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: a meta-analysis. Pharmacogenetics 8:473-479 (1998).
275. A. Rostami-Hodjegan, M. S. Lennard, H. F. Woods, and G. T. Tucker. Meta-analysis of studies of the CYP2D6 polymorphism in relation to lung cancer and Parkinson's disease. Pharmacogenetics 8:227-238 (1998).
276. E. K. Tan, M. Khajavi, J. I. Thornby, S. Nagamitsu, J. Jankovic, and T. Ashizawa. Variability and validity of polymorphism association studies in Parkinson's disease. Neurology 55:533-538 (2000).
277. A. H. Schinkel, E. Wagenaar, C. A. Mol, and L. van Deemter. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacologic activity of many drugs. J. Clin. Invest. 97:2517-2524 (1996).
278. K. L. Mealey, S. A. Bentjen, J. M. Gay, and G. H. Cantor. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 11:727-733 (2001).
279. R. L. Juliano and V. Ling. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455:152-162 (1976).