Drug delivery through the blood-brain barrier

Advanced Drug Delivery Reviews

Volumn 19, Issue 3, 1996, Pages 401-424

  Tamai, Ikumi ^a   Tsuji, Akira ^a  

^a KANAZAWA UNIVERSITY   (Japan)

Author keywords

Absorptive mediated endocytosis; Carrier mediated transport; Monocarboxylic acid transport; P glycoprotein; Peptide transport; Receptor mediated endocytosis

Indexed keywords

AMINES; AMINO ACIDS; BLOOD; BRAIN; CARBOXYLIC ACIDS; DRUG PRODUCTS; IONIC DRUGS; PHARMACODYNAMICS; PROTEINS;

ABSORPTIVE MEDIATED ENDOCYTOSIS; BLOOD BRAIN BARRIER; CARRIER MEDIATED TRANSPORT; GLYCOPROTEIN; MONOCARBOXYLIC ACID SPECIFIC TRANSPORTER; PEPTIDE TRANSPORT; PERMEATION; RECEPTOR MEDIATED ENDOCYTOSIS;

CONTROLLED DRUG DELIVERY;

ARGIPRESSIN; AZELASTINE; CARBOXYLIC ACID; CARRIER PROTEIN; CETIRIZINE; CYCLOSPORIN A; CYPROHEPTADINE; DELTA SLEEP INDUCING PEPTIDE; DYNORPHIN A [1-8][1 (N METHYLTYROSINE) 7 (N METHYLARGININE) 8 DEXTRO LEUCINE N ETHYLAMIDE]; EBIRATIDE; EMEDASTINE; ENKEPHALIN DERIVATIVE; GLYCOPROTEIN P; GONADORELIN; HISTAMINE H1 RECEPTOR ANTAGONIST; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IVERMECTIN; KETOTIFEN; LEUCINE ENKEPHALIN; MEPYRAMINE; MEVINOLIN; PEPTIDE; PEPTIDE DERIVATIVE; PRAVASTATIN; RECEPTOR; SIMVASTATIN; UNINDEXED DRUG; VINBLASTINE;

BLOOD BRAIN BARRIER; BRAIN; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG PENETRATION; DRUG TRANSPORT; ENDOCYTOSIS; HUMAN; MEMBRANE PERMEABILITY; NONHUMAN; PHARMACEUTICS; PRIORITY JOURNAL; REVIEW; TECHNIQUE;

EID: 0030580946     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0169-409X(96)00011-7     Document Type: Review

References (123)

1. [1] Oldendorf, W.H. (1970) Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain Res. 24, 372-376.
2. [2] Kakee, A., Terasaki, T. and Sugiyama, Y. (1995) Organic anion transport system acting as an efflux pump at the blood-brain barrier: Demonstration by a newly developed brain efflux index (BEI) method. Proc. Int. Symp. Control Release Bioact. Mater. 22, 16-18.
3. [3] Ohno, K., Pettigrew, K.D. and Rapoport, S.I. (1978) Lower limits of cerebrovascular permeability to non-electrolytes in the conscious rat. Am. J. Physiol. 235, H229-H307.
4. [4] Zlokovic, B.V., Begley, D.J., Djuricic, B.M. and Mitrovic, D. (1986) Measurement of solute transport across the blood-brain barrier in the perfused guinea pig brain: Method and application to N-methyl-α-aminobutyric acid. J. Neurochem. 46, 1444-1451.
5. [5] Takasato, Y., Rapoport, S.I. and Smith, W.R. (1984) An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am. J. Physiol. 247, H484-H493.
6. [6] Triguero, D., Buciak, J. and Pardridge, W.M. (1990) Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins. J. Neurochem. 54, 1882-1888.
7. [7] Terasaki, T., Deguchi, Y., Sato, H., Hirai, K. and Tsuji, A. (1991) In vitro transport of a dynorphin-like analgesic peptide, E-2078, through the blood-brain barrier: An application of brain microdialysis. Pharm. Res. 8, 815-820.
8. [8] Pardridge, W.M., Eisenberg, J. and Yamada, T. (1985) Rapid sequestration and degradation of somatostatin analogues by isolated brain capillaries. J. Neurochem. 44, 1178-1184.
9. [9] Pardridge, W.M. (1983) Brain metabolism: A perspective from the blood-brain barrier. Physiol. Rev. 63, 1481-1535.
10. [10] Hughes, C.C.W. and Lantos, P.L. (1989) Uptake of leucine and alanine by cultured cerebral capillary endothelial cells. Brain Res. 480, 126-132.
11. [11] Audus, K.L. and Borchardt, R.T. (1986) Characterization of an in vitro blood-brain barrier model system for studying drug transport and metabolism. Pharm. Res. 3, 81-87.
12. [12] Rubin, L.L., Hall, D.E., Porter, S., Barbu, K., Cannon, C., Horner, H.C., Janatpour, M., Liaw, C.W., Manning, K., Morales, J., Tanner, L.I., Tomaselli, K.J. and Bard, F. (1991) A cell culture model of the blood-brain barrier. J. Cell Biol. 115, 1725-1735.
13. [13] Oldendorf, W.H. (1973) Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am. J. Physiol. 224, 1450-1453.
14. [14] Oldendorf, W.H. (1972) Blood-brain barrier permeability to lactate. Eur. Neurol. 6, 49-55.
15. [15] Terasaki, T., Takakuwa, S., Moritani, S. and Tsuji, A. (1991) Transport of monocarboxylic acids at the blood-brain barrier: Studies with monolayers of primary cultured bovine brain capillary endothelial cells. J. Pharmacol. Exp. Ther. 258, 932-937.
16. [16] Terasaki, T., Kang, Y.S., Ohnishi, T. and Tsuji, A. (1991) In vitro evidence for carrier-mediated uptake of acidic drugs by isolated bovine brain capillaries. J. Pharm. Pharmacol. 43, 172-176.
17. [17] Buchalter, S.E., Crain, M.R. and Kreisberg, R. (1989) Regulation of lactate metabolism in vivo. Diabetes Metab. Rev. 5, 379-391.
18. [18] Alm, A. and Tornquist, P. (1985) Lactate transport through blood-retinal and the blood-brain barrier in rats. Ophthalmic Res. 17, 181-184.
19. [19] Aubert, L. and Motaris, R. (1975) Molecular features of organic anion permeability in ox red blood cell. J. Physiol. 246, 159-179.
20. [20] Halestrap, A.P. (1976) Transport of pyruvate and lactate into human erythrocytes. Biochem. J. 156, 193-207.
21. [21] Deuticke, B. (1982) Monocarboxylate transport in erythrocytes. J. Membrane Biol. 70, 89-103.
22. [22] Deuticke, B. (1989) Monocarboxylate transport in red blood cells: Kinetics and chemical modification. Methods Enzymol. 173, 300-329.
23. [23] Poole, R.C. and Halestrap, A.P. (1994) N-Terminal protein sequence analysis of the rabbit erythrocyte lactate transporter suggests identity with the cloned mono-carboxylate transport protein MCT1. Biochem. J. 303, 755-759.
24. [24] Garcia, C.-K., Goldstein, J.L., Pathak, R.K., Anderson, R.G.W. and Brown, M.S. (1994) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the cori cycle. Cell 76, 865-873.
25. [25] Tamai, I., Takanaga, H., Maeda, H., Sai, Y., Ogihara, T., Higashida, H. and Tsuji, A. (1995) Participation of a proton-cotransporter, MCT1 in the intestinal transport mechanism for monocarboxylic acids. Biochem. Biophys. Res. Commun. 214, 482-489.
26. [26] Takanaga, H., Tamai, I., Inaba, S., Sai, Y., Higashida, H., Yamamoto, H. and Tsuji, A. (1995) cDNA Cloning and functional characterization of rat intestinal monocarboxylate transporter. Biochem. Biophys. Res. Commun. 217, 370-377.
27. [27] Henderson, P.J.F. (1993) The 12-transmembrane helix transporters. Curr. Opinion Cell Biol. 5, 708-721.
28. [28] Garcia, C.K., Li, X., Luna, J. and Francke, U. (1994) cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Genomics 23, 500-503.
29. [29] Knudsen, G.M., Paulson, O.B. and Hertz, M.M. (1991) Kinetic analysis of the human blood-brain barrier transport of lactate and its influence by hypercapnia. J. Cerebral Blood Flow Metab. 11, 581-586.
30. [30] Cremer, J.E., Braun, L.D. and Oldendorf, W.H. (1976) Changes during development in transport processes of the blood-brain barrier. Biochim. Biophys. Acta 448, 633-637.
31. [31] Cremer, J.E., Cunningham, V.J., Pardridge, W.M., Braun, L.D. and Oldendorf, W.H. (1979) Kinetics of blood brain barrier transport of pyruvate, lactate and glucose in suckling, weanling and adult rats. J. Neurochem. 33, 439-445.
32. [32] Gjedde, A. and Crone, C. (1975) Induction processes in blood-brain transfer of ketone bodies during starvation. Am. J. Physiol. 229, 1165-1169.
33. [33] Tsuji, A., Saheki, A., Tamai, I. and Terasaki, T. (1993) Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J. Pharmacol. Exp. Ther. 267, 1085-1090.
34. [34] Saheki, A., Terasaki, T., Tamai, I. and Tsuji, A. (1994) In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm. Res. 11, 305-311.
35. [35] Koga, T., Shimada, Y., Kuroda, M., Tsujita, Y., Hasegawa, K. and Yamazaki, M. (1990) Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Biochim. Biophys. Acta 1045, 115-120.
36. [36] Komai, T., Shigehara, E., Tokui, T., Koga, T., Ishigami, M., Kuroiwa, C. and Horiuchi, S. (1992) Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture. Biochem. Pharmacol. 43, 667-670.
37. +-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. Am. J. Physiol. 264, G36-G44.
38. [38] Tamai, I., Takanaga, H., Maeda, H., Ogihara, T., Yoneda, M. and Tsuji, A. (1995) Proton-cotransport of Pravastatin across intestinal brush-border membrane. Pharm. Res. 12, 1727-1732.
39. [39] Kurihara, A., Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1987) Uptake of propranolol by microvessels isolated from bovine brain. J. Pharm. Sci. 76, 759-764.
40. [40] Pardridge, W.M., Sakiyama, R. and Fierer, G. (1982) Transport of propranolol and lidocaine through the rat blood-brain barrier. J. Clin. Invest. 71, 900-908.
41. [41] Kang, Y.S., Terasaki, T., Ohnishi, T. and Tsuji, A. (1990) In vivo and in vitro evidence for a common carrier-mediated transport of choline and basic drugs through the blood-brain barrier. J. Pharmacobio-Dyn. 13, 353-360.
42. [42] Shimon, M., Egozi, Y., Kloog, Y., Sokolovsky, M. and Cohen, S. (1988) Kinetics of choline uptake into isolated rat forebrain microvessels: Evidence of endocrine modulation. J. Neurochem. 50, 1719-1724.
43. [43] Cornford, E.M., Braun, L.D. and Oldendorf, W.H. (1978) Carrier-mediated blood-brain barrier transport of choline and certain choline analogs. J. Neurochem. 30, 299-308.
44. 1-antagonist at the blood-brain barrier: Transport mechanism of mepyramine using carotid injection technique. Biol. Pharm. Bull. 17, 676-679.
45. 1-antagonist at the blood-brain barrier: Mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer culture. Pharm. Res. 11, 975-978.
46. 1-antagonists and lipophilic basic drugs. Pharm. Res. 11, 1516-1518.
47. [47] Banks, W.A., Kastin, A.J. and Barrera, C.M. (1991) Delivering peptides to the central nervous system: Dilemmas and strategies. Pharm. Res. 8, 1345-1350.
48. [48] Banks, W.A. and Kastin, A.J. (1990) Peptide transport systems for opiates across the blood-brain barrier. Am. J. Physiol. 259, E1-E10.
49. [49] Kannan, R., Kuhlenkamp, J.F., Jeandidier, E., Trinh, H., Ookhtens, M. and Kaplowitz, N. (1990) Evidence for carrier-mediated transport of glutathione across the blood-brain barrier in the rat. J. Clin. Invest. 85, 2009-2013.
50. [50] Kannan, R., Kuhlenkamp, J.F., Ookhtens, M. and Kaplowitz, N. (1992) Transport of glutathione at blood-brain barrier of the rat: Inhibition by glutathione analogs and age-dependence. J. Pharmacol. Exp. Ther. 263, 964-970.
51. [51] Lash, L.H. and Jones, D.P. (1984) Renal glutathione transport. Characteristics of the sodium-dependent system in the basolateral membrane. J. Biol. Chem. 259, 14508-14514.
52. [52] Dawson, A.R., Vahakangas, K., Jernstrom, B. and Moldeus, P. (1984) Glutathione conjugation by isolated lung cells and the isolated perfused lung: Effect of extracellular glutathione. Eur. J. Biochem. 13, 439-443.
53. [53] Zlokovic, B.V. (1995) Cerebrovascular permeability to peptides: Manipulations of transport systems at the blood-brain barrier. Pharm. Res. 12, 1395-1406.
54. [54] Yi, J.-R., Lu, S., Fernandez-Checa, J. and Kaplowitz, N. (1994) Expression cloning of a rat hepatic reduced glutathione transporter with canalicular characteristics. J. Clin. Invest. 93, 1841-1845.
55. [55] Rapoport, S.I., Klee, W.A., Pettigrew, K.D. and Ohno, K. (1980) Entry of opioid peptides into the central nervous system. Science 207, 84-86.
56. [56] Zlokovic, B.V., Lipovac, N.M., Begley, D.J., Dacson, H. and Rakic, L. (1987) Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea-pig brain. J. Neurochem. 49, 310-315.
57. [57] Zlokovic, B.V., Mackic, J.B., Djunricic, B. and Davson, H. (1989) Kinetic analysis of leucine-enkephalin cellular uptake at the luminal side of the blood-brain barrier of an in situ perfused guinea-pig brain. J. Neurochem. 53, 1333-1341.
58. [58] Zlokovic B.V., Lipovac, M.N., Begley, D.J., Davson, H. and Rakic, L. (1988) Slow penetration of thyrotropin-releasing hormone across the blood-brain barrier of an in situ perfused guinea pig brain. J. Neurochem. 51, 252-257.
59. [59] Zlokovic, B.V., Hyman, S., McComb, J.G., Lipovac, M.N., Tang, G. and Davson, H. (1990) Kinetics of arginine-vasopressin uptake at the blood-brain barrier. Biochim. Biophys. Acta 1025, 191-198.
60. [60] Barrera, C.M., Kastin, A.J. and Banks, W.A. (1987) D-[Alal]-peptide T-amide is transported from blood to brain by a saturable system. Brain Res. Bull. 19, 629-633.
61. [61] Wilson J.F. (1988) Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive α-melanotropin. Psychopharmacology 96, 262-266.
62. [62] Barrera, C.M., Kastin, A.J., Fasold, M.B. and Banks, W.A. (1991) Bidirectional saturable transport of LHRH across the blood-brain barrier. Am. J. Physiol. 261, E312-E318.
63. 125I-N-Tyr-delta sleeping peptide crosses the blood-brain barrier by a non-competitive mechanism. Brain Res. 301, 201-207.
64. [64] Banks, W.A., Kastin, A.J. and Durham, D.A. (1989) Bidirectional transport of interleukin-1 across the blood-brain barrier. Brain Res. Bull. 23, 433-437.
65. [65] Fei, Y.-J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F.H., Romero, M.F., Singh, S.K., Boron, W.F. and Hediger, M.A. (1994) Expression cloning of a mammalian proton-coupled transporter. Nature 368, 563-566.
66. [66] Miyamoto, K., Shiraga, T., Morita, K., Yamamoto, H., Haga, H., Taketani, Y., Tamai, I., Sai, Y., Tsuji, A. and Takeda, E. (1996) Sequence, tissue distribution and developmental changes in rat intestinal oligopeptide transporter. Biochim. Biophys. Acta 1305, 34-38.
67. [67] Kumagai, A.K., Eisenberg, J. and Pardridge, W.M. (1987) Absorptive-mediated endocytosis of cationized albumin and a β-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. J. Biol. Chem. 262, 15214-15219.
68. [68] Pardridge, W.M., Triguero, D. and Buciak, J. (1989) Transport of histone through the blood-brain barrier. J. Pharmacol. Exp. Ther. 251, 821-826.
69. [69] Terasaki, T., Hirai, K., Sato, H., Kang, Y.S. and Tsuji, A. (1989) Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078, into the blood-brain barrier. J. Pharmacol. Exp. Ther. 251, 351-357.
70. [70] Pardridge, W.M., Triguero, D., Buciak, J. and Yang, J. (1990) Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector. J. Pharmacol. Exp. Ther. 255, 893-899.
71. [71] Pardridge, W.M. (1991) Peptide Drug Delivery to the Brain, Raven Press, New York.
72. [72] Shimura, T., Tabata, S., Ohnishi, T., Terasaki, T. and Tsuji, A. (1991) Transport mechanism of a new behaviorally highly potent adrenocorticotropic hormone (ACTH), through the blood-brain barrier. J. Pharmacol. Exp. Ther., 258, 459-465.
73. [73] Terasaki, T., Takakuwa, S., Saheki, A., Moritani, S., Shiraura, T., Tabata, S. and Tsuji, A. (1992) Absorptive-mediated endocytosis of an adrenocorticotropic hormone (ACTH) analogue, ebiratide, into the blood-brain barrier: Studies with monolayers of primary cultured bovine brain capillary endothelial cells. Pharm. Res. 9, 529-534.
74. [74] Triguero, D., Buciak, J.L. and Pardridge, W.M. (1991) Cationization of immunoglobulin G results in enhanced organ uptake of the protein after intravenous administration in rats and primates. J. Pharmacol. Exp. Ther. 258, 186-192.
75. [75] Smith, K.R. and Borchardt, R.T. (1989) Permeability and mechanism of albumin, cationized albumin, and glycosylated albumin transcellular transport across monolayers of cultured bovine brain capillary endothelial cells. Pharm. Res. 6, 466-473.
76. [76] Nakazawa, T., Furuya, Y., Kaneko, T., Yamatsu, K., Yoshino, H. and Tachibana, S. (1990) Analgesia produced by E-2078, a systemically active dynorphin analog, in mice. J. Pharmacol. Exp. Ther. 252, 1247-1254.
77. [77] Pardridge, W.M., Buciak, J.L. and Friden, P.M. (1991) Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier. J. Pharmacol. Exp. Ther. 259, 66-70
78. [78] Pardridge, W.M., Kumagai, A.K. and Eisenberg, J.B. (1987) Chimeric peptides as a vehicle for peptide pharmaceutical delivery through the blood-brain barrier. Biochem. Biophys. Res. Commun. 146, 307-315.
79. 125I-labeled β-amyloid peptide A-β1-40 through the blood-brain barrier and binding to Alzheimer disease amyloid of the A-β1-40/ vector complex. Proc. Natl. Acad. Sci. USA 92, 10227-10231.
80. [80] Pardridge, W.M., Boado, R.J. and Kang, Y.S. (1995) Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogues through the blood-brain barrier in vivo. Proc. Natl. Acad. Sci. USA 92, 5592-5596.
81. [81] Shin, S.-U., Friden, P., Moran, M., Olson, T., Kang, Y.S., Pardridge, W.M. and Morrison, S.L. (1995) Transferrin-antibody fusion proteins are effective in brain targeting. Proc. Natl. Acad. Sci. USA 92, 2820-2824.
82. [82] Pardridge, W.M., Kang, Y.S., Buciak, J.L. and Yang, J. (1995) Human insulin receptor monoclonal antibody undergoes high affinity binding to human brain capillaries in vitro and rapid transcytosis through the blood-brain barrier in vivo in the primate. Pharm. Res. 12, 807-816.
83. [83] Jefferies, A.A., Brandon, M.R., Hunt, S.V., Williams, A.F., Gatter, K.C. and Mason, D.Y. (1984) Transferrin receptor on endothelium of brain capillary. Nature 312, 162-163.
84. [84] Friden, P.M., Walus, L.R., Musso, G.F., Taylor, M.A., Malfroy, B. and Starzyk, R.M. (1991) Anti-transferrin receptor antibody and antibody-drug conjugate cross the blood-brain barrier. Proc. Natl. Acad. Sci. USA 88, 4771-4775.
85. [85] Pardridge, W.M. (1995) Blood-brain barrier peptide transport and peptide drug delivery to the brain. In: M.D. Taylor and G.L. Amidon (Eds.), Peptide-based Drug Design. pp. 265-296, American Chemical Society, Washington, DC.
86. [86] Tsuzuki, N., Hama, T., Hibi, T., Konishi, R., Futaki, S. and Kitagawa, K. (1991) Adamantanes as a brain-directed drug carrier for poorly absorbed drug: Antinociceptive effects of [D-ala2]leu-enkephalin derivatives conjugated with the 1-adamantane moiety. Biochem. Pharmacol. 41, R5-R8.
87. [87] Bodor, N., Prokai, L., Wu, W.M., Farag, H., Jonalagadda, S., Kawamura, M. and Simpkins, J. (1992) A strategy for delivering peptides into the central nervous system by sequential metabolism. Science 257, 1698-1700.
88. [88] Cornford, E.M. (1985) The blood-brain barrier, a dynamic regulatory interface. Mol. Physiol. 7, 219-260.
89. [89] Levin, V.A. (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability J. Med. Chem. 23, 682-684.
90. [90] Pardridge, W.M., Triguero, D., Yang, J. and Cancilla, P.A. (1990) Comparison of in vitro and in vivo models of drug transcytosis through the blood-brain barrier. J. Pharmacol. Exp. Ther. 253, 884-891.
91. [91] Biedler, J.L. and Riehm, H. (1970) Cellular resistance to actinomycin D in Chinese hamster cells in vitro: Cross-resistance, radioautographic, and cytogenetic studies. Cancer Res. 30, 1174-1184.
92. [92] Juliano, R.L. and Ling, V. (1976) Surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455, 152-162.
93. [93] Bradley, G., Juranka, P.F. and Ling, V. (1989) Mechanism of multidrug resistance. Biochim. Biophys. Acta 948, 87-128.
94. [94] Skovsgaard, T. (1978) Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cell. Cancer Res. 38, 4722-4727.
95. [95] Gross, P., Neriah, Y.B., Croop, J.M. and Housman, D.E. (1986) Isolation and expression of complementary DNA that confers multidrug resistance. Nature 323, 728-731.
96. [96] Safa, A.R. Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. (1989) Proc. Natl. Acad. Sci. USA 85, 7187-7191.
97. [97] Tamai, I. and Safa, A.R. (1991) Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. J. Biol. Chem. 266, 16796-16800.
98. [98] Safa, A.R., Glover, C.J., Meyers, M.B., Biedler, J.L. and Felsted, R.L. (1986) Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J. Biol. Chem. 261, 6137-6140.
99. [99] Endicott, J.A. and Ling. V. (1989) The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 58, 137-171.
100. [100] Gross, P., Raymond, M., Bell, J. and Housman, D. (1988) Cloning and characterization of a second member of the mouse mdr gene family. Mol. Cell Biol. 8, 2770-2778.
101. [101] Silverman, J.A., Raunio, H., Gant, T.W. and Thorgeirsson, S.S. (1991) Cloning and characterization of the rat multidrug resistance (mdr) gene family. Gene 106, 229-236.
102. [102] Brown, P.C., Thorgeirsson, S.S. and Silverman, J.A. (1993) Cloning and regulation of the rat mdr2 gene. Nucl. Acids Res. 21, 3885-3891.
103. [103] Smit, J.J., Schinkel, A.H., Oude Elferink, R.P.J., Groen, A.K., Wagenaar, E., van Deemter, L., Mol, C.A.A.M., Ottenhoff, R., van der Lugt, N.M.T., van Roon, M.A., van der Valk, M.A., Offerhaus, G.J.A., Berns, A.J.M. and Borst, P. (1993) Hozygous 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.
104. [104] Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I. and Willingham, M. (1987) Cellular localization of the multidrug-resistance gene P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 84, 7735-7738.
105. [105] Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I. and Willingham, M.C. (1989) Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: Evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 37, 159-164.
106. [106] Cordon-Cardo, C., O'Brien, J.P., Casals, D., Rittaman-Grauer, L., Biedler, J.L., Melamed, M.R. and Bertino, J.R. (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. USA 86, 695-698.
107. [107] Watanabe, T., Miyauchi, S., Sawada, Y., Iga, T., Hanano, M., Inaba, M. and Sugiyama, Y. (1992) Kinetic analysis of hepatobiliary transport of vincristine. J. Hepatol. 16, 77-88.
108. [108] Tanigawara, Y., Okamura, N., Hirai, M., Yasuhara, M., Ueda, K., Kioka, N., Komano, T. and Hori, R. (1992) Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J. Pharmacol. Exp. Ther. 263, 840-845.
109. [109] Schinkel, A.H., Mol, C.A.A.M., Wagenaar, E., van Deemter, L., Smit, J.J.M. and Borst, P. (1995) Multidrug resistance and the role of P-glycoprotein knockout mice. Eur. J. Cancer 31A, 1295-1298.
110. [110] Tsuji, A., Terasaki, T., Takabatake, Y., Tenda, Y., Tamai, I., Yamashima, T., Moritani, S., Tsuruo, T. and Yamashita, J. (1992) P-Glycoprotein as the drug efflux pump in primary cultured brain capillary endothelial cells. Life Sci. 51, 1427-1437.
111. [111] Tatsuta, T., Naito, M., Oh-hara, T., Sugawara, I. and Tsuruo, T. (1992) Functional involvement of P-glycoprotein in blood-brain barrier. J. Biol. Chem. 267, 20383-20391.
112. [112] Greenwood, J. (1992) 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.
113. [113] Hegmann, E.J., Bauer, H.C. and Kerbel, R.S. (1992) Expression and functional activity of P-glycoprotein in cultured cerebral capillary endothelial cells. Cancer Res. 52, 6969-6975.
114. [114] Jette, L., Tetu, B. and Beliveau, R. (1993) High levels of P-glycoprotein detected in isolated brain capillaries. Biochim. Biophys. Acta 1150, 147-154.
115. [115] Sakata, A., Tamai, I., Kawazu, K., Deguchi, Y., Ohnishi, T., Saheki, A. and Tsuji, A. (1994) In vivo evidence for ATP-dependent and P-glycoprotein-mediated transport of cyclosporin A at the blood-brain barrier. Biochem. Pharmacol. 48, 1989-1992.
116. [116] Schinkel, A.H., Smit, J.J.M., van Tellingen, O., Beijnen, J.H., Wagenaar, E., van Deemter, L., Mol, C.A.A.M., van der Valk, M.A., Robanus-Maandag, E.C., te Ricle, H.P.J., Berns, A.J.M. and Borst, P. (1994) 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.
117. [117] Ohnishi, T., Tamai, I., Sakanaka, K., Sakata, A., Yamashima, T., Yamashita, J. and Tsuji, A. (1995) 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.
118. [118] Wang, Q., Yang, H., Miller, D.W. and Elmquist, W.F. (1995) 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.
119. [119] Pulsinelli, W.A. and Duffy, T.E. (1983) Regional energy balance in rat brain after transient forebrain ischemia. J. Neurochem. 40, 1500-1503.
120. [120] Tamai, I. and Safa, A.R. (1990) Competitive interaction of cydosporins with the Vinca alkaloid-binding site of P-glycoprotein in multidrug resistant cells. J. Biol. Chem. 265, 16509-16513.
121. [121] Schinkel, A.H., Wagenaar, E., van Deemter, L., Mol, C.A.A.M. and Borst, P. (1995) Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest. 96, 1698-1705.
122. [122] Tsuji, A., Tamai, I., Sakata, A., Tenda, Y. and Terasaki, T. (1993) Restricted transport of cyclosporin A across the blood-brain barrier by a multidrug transporter, P-glycoprotein. Biochem. Pharmacol. 46, 1096-1099.
123. [123] Shirai, A., Naito, M., Tatsuta, T., Dong, J., Hanaoka, K., Mikami, K., Oh-hara, T. and Tsuruo, T. (1994). Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein. Biochim. Biophys. Acta 1222, 400-404.