Skip to main content

Drug Disposition and Targeting

Transport across the Blood-Brain Barrier

  • Chapter
Membrane Transporters as Drug Targets

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 12))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adkison, K. D., and Shen, D. D., 1996, Uptake of valproic acid into rat brain is mediated by a medium-chain fatty acid transporter, J. Pharmacol. Exp. Ther. 276: 1189–1200.

    PubMed  CAS  Google Scholar 

  • Agus, D. B., Gambhir, S. S., Pardridge, W. M., Spielholz, C., Baselga, J., Vera, J. C., and Golde, D. W., 1997, Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters, J. Clin. Invest. 100:2842–2848.

    PubMed  CAS  Google Scholar 

  • Audus, K. L., and Borchardt, R. T., 1991, Transport of macromolecules across the capillary endothelium, Handbook Exp. Pharmacol. 100:43–70.

    CAS  Google Scholar 

  • Audus, K. L., Chikhale, P. J., Miller, D. W., Thompson, S. E., and Borchardt, R. T., 1992, Brain uptake of drugs: The influence of chemical and biological factors, Adv. Drug Res. 23:1–64.

    CAS  Google Scholar 

  • Audus, K. L., Ng, L., Wang, W., and Borchardt, R. T., 1996, Brain microvessel endothelial cell culture systems, Pharmaceut. Biotechnol. 8:239–258.

    CAS  Google Scholar 

  • Banks, W. A., and Broadwell, R. D., 1994, Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin, and albumin: Pharmacokinetic and morphological assessments, J. Neurochem. 62:2404–2419.

    PubMed  CAS  Google Scholar 

  • Banks, W. A., and Kastin, A. J., 1996, Passage of peptides across the blood-brain barrier: Pathophysiological perspectives, Life Sci. 59:1923–1943.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., and Kastin, A. J., 1997, The role of the blood-brain barrier transporter PTS-1 in regulating concentrations of methionine enkephalin in blood and brain, Alcohol 14:237–245.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Kastin, A. J., Horvath, A., and Michals, E. A., 1987, Carrier-mediated transport of vasopressin across the blood-brain barrier of the mouse, J. Neurosci. Res. 18:326–332.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Kastin, A. J., Sam, H. M., Cao, V. T., King, B., Maness, L. M., and Schally, A. V., 1994, Saturable efflux of the peptides RC-160 and Tyr-MIF-1 by different parts of the blood-brain barrier, Brain Res. Bull. 35:179–182.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Wustrow, D. J., Cody, W. L., Davis, M. D., and Kastin, A. J., 1995, Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1, Brain Res. 695:59–63.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., and Maness, L. M., 1996, Leptin enters the brain by a saturable system independent of insulin, Peptides 17:305–311.

    Article  PubMed  CAS  Google Scholar 

  • Barrand, M. A., Bagrij, T., and Neo, S. Y., 1997, Multidrug resistance-associated protein: A protein distinct from P-glycoprotein involved in cytotoxic drug expulsion. Gen. Pharmacol. 28:639–645.

    PubMed  CAS  Google Scholar 

  • Barrera, C. M., Kastin, A. J., and Banks, W. A., 1987, d-[Ala1]-peptide T-amide is transported from blood to brain by a saturable system, Brain Res. Bull. 19:629–633.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Begley, D. J., 1996, The blood-brain barrier: Principles for targeting peptides and drugs to the central nervous system, J. Pharm. Pharmacol. 48:136–146.

    PubMed  CAS  Google Scholar 

  • Benrabh, H., and Lefauconnier, J. M., 1996, Glutamate is transported across the rat blood-brain barrier by a sodium-independent system, Neurosci. Lett. 210:9–12.

    Article  PubMed  CAS  Google Scholar 

  • Berger, W., Hauptmann, E., Elbling, L., Vetterlein, M., Kokoschka, E. M., and Micksche, M., 1997, Possible role of the multidrug resistance-associated protein (MRP) in chemoresistance of human melanoma cells, Int. J. Cancer 71:108–115.

    PubMed  CAS  Google Scholar 

  • Boado, R. J., 1995, Brain-derived peptides regulate the steady state levels and increase stability of the blood-brain barrier GLUT1 glucose transporter mRNA, Neurosci. Lett. 197:179–182.

    Article  PubMed  CAS  Google Scholar 

  • Bradbury, M. W., 1997, Transport of iron in the blood-brain-cerebrospinal fluid system, J. Neurochem. 69:443–454.

    PubMed  CAS  Google Scholar 

  • Brightman M. W., and Reese, T. S., 1969, Junctions between intimately apposed cell membranes in the vertebrate brain, J. Cell. Biol. 40:648–677.

    Article  PubMed  CAS  Google Scholar 

  • Broadwell, R. D., and Banks, W. A., 1993, A cell biological perspective for the transcytosis of peptides and proteins through the mammalian blood-brain fluid barriers, in: The Blood-Brain Barrier: Cellular and Molecular Biology (W. M. Pardridge, ed.), Raven Press, New York, pp. 165–199.

    Google Scholar 

  • Broadwell, R. D., Baker-Cairns, B. J., Friden, P. M., Oliver, C., and Villegas, J. C., 1996, Transcytosis of protein through the mammalian cerebral epithelium and endothelium III. Receptor-mediated transcytosis through the blood-brain barrier of blood-borne transferrin and antibody against the transferrin receptor, Exp. Neurol. 142:47–65.

    Article  PubMed  CAS  Google Scholar 

  • Burt, R. K., and Thorgeirsson, S. S., 1988, Coinduction of MDR-1 multidrug-resistance and cytochrome P-450 genes in rat liver by xenobiotics, J. Natl. Cancer. Inst. 80:1383–1386.

    PubMed  CAS  Google Scholar 

  • Chikhale, E. G., Chikhale, P. J., and Borchardt, R. T., 1995a, Carrier-mediated transport of the antitumor agent acivicin across the blood-brain barrier, Biochem. Pharmacol. 49:941–945.

    Article  PubMed  CAS  Google Scholar 

  • Chikhale, E. G., Burton, P. S. and Borchardt, R. T., 1995b, The effect of verapamil on the transport of peptides across the blood-brain barrier in rats: Kinetic evidence for an apically polarized efflux mechanism, J. Pharmacol. Exp. Ther. 273:298–303.

    PubMed  CAS  Google Scholar 

  • Claudio, L., Raine, C. S., and Brosnan, C. F., 1995, Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis, Acta Neuropathol. Berl. 90:228–38.

    PubMed  CAS  Google Scholar 

  • Conn, A. R., Fell, D. I., and Steele, R. D., 1983, Characterization of alpha-keto acid transport across blood-brain barrier in rats, Am. J. Physiol. 245:E253–E260.

    PubMed  CAS  Google Scholar 

  • Cornford, E. M., and Oldendorf, W. H., 1975, Independent blood-brain barrier transport systems for nucleic acid precursors, Biochim. Biophys. Acta 394:211–219.

    PubMed  CAS  Google Scholar 

  • Crone, C., and Olesen, S. P., 1982, Electrical resistance of brain microvascular endothelium, Brain Res. 241:49–55.

    Article  PubMed  CAS  Google Scholar 

  • De Boer, A. G., and Breimer, D. D., 1994, The bloodbrain barrier: Clinical implications for drug delivery to the brain, J. R. Coll. Physicians 28:502–506.

    Google Scholar 

  • Dehouck, B., Fenart, L., Dehouck, M. P., Pierce, A., Torpier, G., and Cecchelli, R., 1997, A new function for the LDL receptor: Transcytosis of LDL across the blood-brain barrier, J. Cell Biol. 138:877–889.

    Article  PubMed  CAS  Google Scholar 

  • Drion, N., Lemaire, M., Lefauconnier, J. M., and Scherrmann, J. M., 1996, Role of P-gly-coprotein in the blood-brain transport of colchicine and vinblastine, J. Neurochem. 67:1688–1693.

    PubMed  CAS  Google Scholar 

  • Drori, S., Eytan, G. D., and Assaraf, Y. G., 1995, 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.

    Article  PubMed  CAS  Google Scholar 

  • Duffy, K. R., and Pardridge, W. M., 1987, Blood-brain barrier transcytosis of insulin in developing rabbits, Brain Res. 420:32–38.

    Article  PubMed  CAS  Google Scholar 

  • Fiori, A., Cardelli, P., Negri, L., Savi, M. R., Strom, R., and Erspamer, V., 1997, Deltorphin transport across the blood-brain barrier, Proc. Natl. Acad. Sci. USA 94:9469–9474.

    Article  PubMed  CAS  Google Scholar 

  • Friden, P. M., 1994, Receptor-mediated transport of therapeutics across the blood-brain barrier, Neurosurgery 35:294–298.

    PubMed  CAS  Google Scholar 

  • Friden, P. M., Olson, T. S., Obar, R., Walus, L. R., and Putney, S. D., 1996, Characterization, receptor mapping and blood-brain barrier transcytosis of antibodies to the human transferrin receptor, J. Pharmacol. Exp. Ther. 278:1491–1498.

    PubMed  CAS  Google Scholar 

  • Fukuta, M., Okada, H., Iinuma, S., Yanai, S., and Toguchi, H., 1994, Insulin fragments as a carrier for peptide delivery across the blood-brain barrier, Pharmaceut. Res. 11:1681–1688.

    Article  CAS  Google Scholar 

  • Galea, E., and Estrada, C., 1992, Ouabain-sensitive choline transport system in capillaries isolated from bovine brain, J. Neurochem. 59:936–941.

    PubMed  CAS  Google Scholar 

  • Gerhart, D. Z., Enerson, B. E., Zhdankina, O. Y., Leino, R. L. and Drewes, L. R., 1997, Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats, Am. J. Physiol. 273:E207–E213.

    PubMed  CAS  Google Scholar 

  • Germann, U. A., Ford, P. J., Shlyakhter, D., Mason, V. S., and Harding, M. W., 1997, Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP, Anticancer Drugs 8:141–155.

    PubMed  CAS  Google Scholar 

  • Ghersi-Egea, J. F., Leininger-Muller, B., Cecchelli, R., and Fenstermacher, J. D., 1995, Blood-brain interfaces: Relevance to cerebral drug metabolism, Toxicol. Lett. 82–83:645–653.

    PubMed  Google Scholar 

  • Golden, P. L., Maccagnan, T. J., and Pardridge, W. M., 1997, Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels, J. Clin. Invest. 99:14–18.

    PubMed  CAS  Google Scholar 

  • Gottesman, M. M., and Pastan, I., 1993, Biochemistry of multidrug resistance mediated by the multidrug transporter, Annu. Rev. Biochem. 62:385–427.

    Article  PubMed  CAS  Google Scholar 

  • Gragera, R. R., Muniz, E., and Martinez-Rodriguez, R., 1993, Molecular and ultrastructural basis of the blood-brain barrier function. Immunohistochemical demonstration of Na+/K+ ATPase, alpha-actin, phosphocreatine and clathrin in the capillary wall and its microenvironment, Cell. Mol. Biol. 39:819–828.

    PubMed  CAS  Google Scholar 

  • Greenwood, J., Love, E. R., and Pratt, O. E., 1982, Kinetics of thiamine transport across the blood-brain barrier in the rat, J. Physiol. (London) 327:95–103.

    CAS  Google Scholar 

  • Halmos, T., Santarromana, M., Antonakis, K., and Scherman, D., 1996, Synthesis of glucose-chlorambucil derivatives and their recognition by the human GLUT1 glucose transporter, Eur. J. Pharmacol. 318:477–484.

    Article  PubMed  CAS  Google Scholar 

  • Hokari, M., Wu, H. Q., Schwarcz, R., and Smith, Q. R., 1996, Facilitated brain uptake of 4-chlorokynurenine and conversion to 7-chlorokynurenic acid, Neuro Report 8:15–18.

    CAS  Google Scholar 

  • Honkanen, R. A., McBath, H., Kushmerick, C., Callender, G. E., Scarlata, S. F., Fenstermacher, J. D., and Haspel, H. C., 1995, Barbiturates inhibit hexose transport in cultured mammalian cells and human erythrocytes and interact directly with purified GLUT-1, Biochemistry 34:535–544.

    Article  PubMed  CAS  Google Scholar 

  • Huang, Y., Ibrado, A. M., Reed, J. C., Bullock, G., Ray, S., Tang, C., and Bhalla, K., 1997, Coexpression of several molecular mechanisms of multidrug resistance and their significance for paclitaxel cytotoxicity in human AML HL-60 cells, Leukemia 11:253–257.

    Article  PubMed  CAS  Google Scholar 

  • Izquierdo, M. A., Neefjes, J. J., Mathari, A. E., Flens, M. J., Scheffer, G. L., and Scheper, R. J., 1996, Overexpression of the ABC transporter TAP in multidrug-resistant human cancer cell lines, Br. J. Cancer 74:1961–1967.

    PubMed  CAS  Google Scholar 

  • Jette, L., Murphy, G. F., Leclerc, J. M., and Beliveau, R., 1995, Interaction of drugs with P-glycoprotein in brain capillaries, Biochem. Pharmacol. 50:1701–1709.

    Article  PubMed  CAS  Google Scholar 

  • Joo, F., 1996, Endothelial cells of the brain and other organ systems: Some similarities and differences, Prog. Neurobiol. 48:255–273.

    Article  PubMed  CAS  Google Scholar 

  • Kannan, R., Yi, J. R., Tang, D., Li, Y., Zlokovic, B. V., and Kaplowitz, N., 1996, Evidence for the existence of a sodium-dependent glutathione (GSH) transporter, J. Biol. Chem. 271:9754–9758.

    PubMed  CAS  Google Scholar 

  • Kavallaris, M., 1997, The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance, Anticancer Drugs 8:17–25.

    PubMed  CAS  Google Scholar 

  • Keep, R. F., and Xiang, J., 1995, N-system amino acid transport at the blood-CSF barrier, J. Neurochem. 65:2571–2576.

    PubMed  CAS  Google Scholar 

  • Komura, J., Tamai, I., Senmaru, M., Terasaki, T., Sai, Y., and Tsuji, A., 1996, Sodium and chloride-dependent transport of beta-alanine across the blood-brain barrier, J. Neurochem. 67:330–335.

    PubMed  CAS  Google Scholar 

  • Kumagai, A. K., Eisenberg, J. B., and Pardridge, W. M., 1987, Adsorptive-mediated endocytosis of cationized albumin and a □-endorphin-cationized albumin chimeric peptide by isolated brain capillaries, J. Biol. Chem. 262:15214–15219.

    PubMed  CAS  Google Scholar 

  • Lee, J. S., Scala, S., Matsumoto, Y., Dickstein, B., Robey, R., Zhan, Z., Altenberg, G., and Bates, S. E., 1997, Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoprotein or MRP overexpression, J. Cell. Biochem. 65:513–526.

    Article  PubMed  CAS  Google Scholar 

  • Lee, W. J., Hawkins, R. A., Peterson, D. R., and Vina, J. R., 1996, Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier, J. Biol. Chem. 271:19129–19133.

    PubMed  CAS  Google Scholar 

  • Lum, B. L., and Gosland, M. P., 1995, MDR expression in normal tissues. Pharmacologic implications for the clinical use of P-glycoprotein inhibitors, Hematol. Oncol. Clin. 9:319–336.

    CAS  Google Scholar 

  • Martins, J. M., Kastin, A. J., and Banks, W. A., 1996, Unidirectional specific and modulated brain to blood transport of corticotropin-releasing hormone, Neuroendocrinology 63:338–343.

    PubMed  CAS  Google Scholar 

  • Martins, J. M., Banks, W. A., and Kastin, A. J., 1997, Acute modulation of active carrier-mediated brain-to-blood transport of corticotropin-releasing hormone, Am. J. Physiol. 272:E312–E319.

    PubMed  CAS  Google Scholar 

  • Ment, L. R., Stewart, W. B., Ardito, T. A., and Madri, J. A., 1995, Germinal matrix microvascular maturation correlates inversely with the risk period for neonatal intraventricular hemorrhage, Brain Res. Dev. Brain Res. 84:142–149.

    PubMed  CAS  Google Scholar 

  • Miller, D. W., Han, H. Y., and Carney, D., 1997, Is the probenecid-sensitive transporter in the blood-brain barrier multidrug resistance associated protein (MRP)? Pharmaceut. Res. 14:332.

    Article  Google Scholar 

  • Minn, A., Ghersi-Egea, J. F., Perrin, R., Leininger, B., and Siest, G., 1991, Drug metabolizing enzymes in the brain and cerebral microvessels, Brain Res. l6:65–82.

    Google Scholar 

  • Mroczkowska, J. E., Galla, H. J., Nalecz, M. J., and Nalec, K. A., 1997, Evidence for an asymmetrical uptake of l-carnitine in the blood-brain barrier in vitro, Biochem. Biophys. Res. Commun. 241:127–131.

    Article  PubMed  CAS  Google Scholar 

  • Nishizaki, T., Kammesheidt, A., Sumikawa, K., Asada, T., and Okada, Y., 1995, A sodium-and energy-dependent glucose transporter with similarities to SGLT1-2 is expressed in bovine cortical vessels, Neurosci. Res. 22:13–22.

    Article  PubMed  CAS  Google Scholar 

  • Oldendorf, W. H., 1971, Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection, Am. J. Physiol. 221:1629–1639.

    PubMed  CAS  Google Scholar 

  • Oldendorf, W. H., and Szabo, J., 1976, Amino acid assignment to one of three blood-brain carrier amino acid carriers, Am. J. Physiol. 230:94–98.

    PubMed  CAS  Google Scholar 

  • Oldendorf, W. H., Hyman, S., Braun, L. D., and Oldendorf, S. Z., 1972, Blood-brain barrier: Penetration of morphine, codeine, heroin, and methadone after carotid injection, Science 178:984.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., 1979, Carrier mediated transport of thyroid hormones through the blood-brain barrier. Primary role of albumin bound hormone, Endocrinology 105:605–612.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W. M., 1983, Brain metabolism: A perspective from the blood-brain barrier, Physiol. Rev. 63:1481–1535.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., 1994, New approaches to drug delivery through the blood-brain barrier, Trends Biotechnol. 12:239–245.

    Article  PubMed  CAS  Google Scholar 

  • 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. 146:307–313.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W. M., Triguero, D., and Buciak, J., 1989, Transport of histone through the blood-brain barrier, J. Pharmacol. Exp. Ther. 251:821–826.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., Boado, R. J., and Farrell, C. R., 1990, Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier. Studies with quantitative western blotting and in situ hybridization, J. Biol. Chem. 265:18035–18040.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., Kang, Y. S., and Buciak, J. L., 1994, Transport of human recombinant brain-derived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery, Pharmaceut. Res. 11:738–746.

    Article  CAS  Google Scholar 

  • Pardridge, W. M., Boado, R. J., and Kang, Y. S., 1995a, Vector-mediated delivery of a polyamide (“peptide”) nucleic acid analogue through the blood-brain barrier in vivo, Proc. Natl. Acad. Sci. USA 92:5592–5596.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., Kang, Y. S., Buciak, J. L., and Yang, J., 1995b, 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, Pharmaceut. Res. 12:807–816.

    Article  CAS  Google Scholar 

  • Pardridge, W. M., Golden, P. L., Kang, Y. S., and Bickel, U., 1997, Brain microvascular and astrocyte localization of P-glycoprotein, J. Neurochem. 68:1278–1285.

    PubMed  CAS  Google Scholar 

  • Plotkin, S. R., Banks, W. A., Waguespack, P. J., and Kastin, A. J., 1997, Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide transport system-1 in-dependent of preproenkephalin mRNA, J. Neurosci. Res. 48:273–280.

    Article  PubMed  CAS  Google Scholar 

  • Poduslo, J. F., Curran, G. L., and Berg, C. T., 1994, Macromolecular permeability across the blood-nerve and blood-brain barriers, Proc. Natl. Acad. Sci. USA 91:5705–5709.

    PubMed  CAS  Google Scholar 

  • Poduslo, J. F., Curran, G. L., Haggard, J. J., Biere, A. L., and Selkoe, D. J., 1997, Permeability and residual plasma volume of human, Dutch variant, and rat amyloid beta-protein 1–40 at the blood-brain barrier, Neurobiol. Dis. 4:27–34.

    Article  PubMed  CAS  Google Scholar 

  • Polt, R., Porreca, F., Szabo, L, Z., Bilsky, E. J., Davis, P., Abbruscato, T. J., Davis, T. P., Harvath, R., Yamamura, H. I., and Hruby V. J., 1994, Glycopeptide enkephalin analogues produce analgesia in mice: Evidence for penetration of the blood-brain barrier, Proc. Natl. Acad. Sci. USA 91:7114–7118.

    PubMed  CAS  Google Scholar 

  • Reese, T. S., and Karnovsky, M. J., 1967, Fine structural localization of a blood-brain barrier to exogenous peroxidase, J. Cell. Biol. 34:207–217.

    Article  PubMed  CAS  Google Scholar 

  • Reichel, A., Begley, D. J., and Ermisch, A., 1996, Arginine vasopressin reduces the blood-brain barrier transfer of l-tyrosine and l-valine: Further evidence of the effect of the peptide on the L-system transporter at the blood-brain barrier, Brain Res. 713:232–239.

    Article  PubMed  CAS  Google Scholar 

  • Reinhardt, R. R., and Bondy, C. A., 1994, Insulin-like growth factors cross the blood-brain barrier, Endocrinology 135:1753–1761.

    Article  PubMed  CAS  Google Scholar 

  • Sanchez del Pino, M. M., Peterson, D. R., and Hawkins, R. A., 1995, Neutral amino acid transport characterization of isolated luminal and abluminal membranes of the blood-brain barrier, J. Biol. Chem. 270:14913–14918.

    PubMed  CAS  Google Scholar 

  • Sarkadi, B., Muller, M., Homolya, L., Hollo, Z., Seprodi, J., Germann, U. A., Gottesman, M. M., Price, E. M., and Boucher, R. C., 1994, Interaction of bioactive hydrophobic peptides with the human multidrug transporter, FASEB J. 8:766–770.

    PubMed  CAS  Google Scholar 

  • Schinkel, A. H., Smit, J. J. M., van Tellingen, O., Breijnen, J. H., Wagenaar, E., Van Deemter, L., Mol, C. A. A. M., van der Valk, M. A., Robanus-Maanday, E. C., te Riele, H. P. J., et al., 1994, Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs, Cell 77:491–502.

    Article  PubMed  CAS  Google Scholar 

  • Schinkel, A. H., Wagenaar, E., Mol, C. A., and van Deemter, L., 1996, P-Glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs, J. Clin. Invest. 97:2517–2524.

    Article  PubMed  CAS  Google Scholar 

  • Sharma, R. C., Inoue, S., Roitelman, J., Schimke, R. T., and Simoni, R. D., 1992, Peptide transport by the multidrug resistance pump, J. Biol. Chem. 267:5731–5734.

    PubMed  CAS  Google Scholar 

  • Sharom, F. J., Yu, X., Chu, J. W., and Doige, C. A., 1995, Characterization of the ATPase activity of P-glycoprotein from multidrug-resistant Chinese hamster ovary cells, Biochem. J. 308:381–390.

    PubMed  CAS  Google Scholar 

  • Shi, F., Bailey, C., Malick, A. W., and Audus, K. L., 1993, Biotin uptake and transport across bovine brain microvessel endothelial cell monolayers, Pharmaceut. Res. 10:282–288.

    Article  CAS  Google Scholar 

  • Shulkin, B. L., Betz, A. L., Koeppe, R. A., and Agranoff, B. W., 1995, Inhibition of neutral amino acid transport across the human blood-brain barrier by phenylalanine, J. Neurochem. 64:1252–1257.

    PubMed  CAS  Google Scholar 

  • Silverman, J. A., and Schrenk, D., 1997, Hepatic cannicular membrane 4: Expression of the multidrug resistance genes in the liver, FASEB J. 11:308–313.

    PubMed  CAS  Google Scholar 

  • Smith, Q. R., 1996, Brain perfusion systems for studies of drug uptake and metabolism in the central nervous system, Pharmaceut. Biotechnol. 8:285–308.

    CAS  Google Scholar 

  • Smith, Q. R., Nagura, H., Takada, Y., and Duncan, M. W., 1992, Facilitated transport of the neurotoxin, beta-N-methylamino-l-alanine, across the blood-brain barrier, J. Neurochem. 58:1330–1337.

    PubMed  CAS  Google Scholar 

  • Spector, R., Sivesind, C., and Kinzenbaw, D., 1986, Pantothenic acid transport through the blood-brain barrier, J. Neurochem. 47:966–971.

    PubMed  CAS  Google Scholar 

  • Stein, W. D., 1997, Kinetics of the multidrug transporter (P-glycoprotein) and its reversal, Physiol. Rev. 77:545–590.

    PubMed  CAS  Google Scholar 

  • Stewart, P. A., Beliveau, R., and Rogers, K. A., 1996, Cellular localization of P-glycoprotein in brain versus gonadal capillaries, J. Histochem. Cytochem. 44:679–685.

    PubMed  CAS  Google Scholar 

  • Takada, Y., Vistica, D. T., Greig, N. H., Purdon, D., Rapoport, S. I., and Smith, Q. R., 1992, Rapid high-affinity transport of a chemotherapeutic amino acid across the blood-brain barrier, Cancer Res. 52:2191–2196.

    PubMed  CAS  Google Scholar 

  • Takanaga, H., Tamai, I., and Tsuji, A., 1994, pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells, J. Pharm. Pharmacol. 46:567–570.

    PubMed  CAS  Google Scholar 

  • Tamai, I., Senmaru, M., Terasaki, T., and Tsuji, A., 1995, Na(+)-and Cl(-)-dependent transport or taurine at the blood-brain barrier, Biochem. Pharmacol. 50:1783–1793.

    Article  PubMed  CAS  Google Scholar 

  • Tamai, I., Sai, Y., Kobayashi, H., Kamata, M., Wakamiya, T., and Tsuji, A., 1997, Structure-internalization relationship for adsorptive-mediated endocytosis of basic peptides at the blood-brain barrier, J. Pharmacol. Exp. Ther. 280:410–415.

    PubMed  CAS  Google Scholar 

  • Thomas, S. A., and Segal, M. B., 1997, The passage of azidodeoxythymidine into and within the central nervous system: Does it follow the parent compound, thymidine, J. Pharmacol. Exp. Ther. 281:1211–1218.

    PubMed  CAS  Google Scholar 

  • Thomas, S. A., Abbruscato, T. J., Hruby, V. J., and Davis, T. P., 1997, The entry of [d-penicillamine2,5]enkephalin into the central nervous system: Saturation kinetics and specificity, J. Pharmacol. Exp. Ther. 280:1235–1240.

    PubMed  CAS  Google Scholar 

  • Thorens, B., 1996, Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes, Am. J. Physiol. 270:G541–G553.

    PubMed  CAS  Google Scholar 

  • Thorgeirsson, S. S., Silverman, J. A., Gant, T. W., and Marino, P. A., 1991, Multidrug resistance gene family and chemical carcinogens, Pharmacol. Ther. 49:283–292.

    Article  PubMed  CAS  Google Scholar 

  • Villegas, J. C., and Broadwell, R. D., 1993, Transcytosis of protein through the mammalian cerebral epithelium and endothelium: II. Adsorptive transcytosis of WGA-HRP and the blood-brain barriers, J. Neurocytol. 22:67–80.

    Article  PubMed  CAS  Google Scholar 

  • Vorbrodt, A. W., and Trowbridge, R. S., 1991, Ultrastructural study of transcellular transport of native and cationized albumin in cultured sheep brain microvascular endothelium, J. Neurocytol. 20:998–1006.

    Article  PubMed  CAS  Google Scholar 

  • Wigler, P. W., 1996, Cellular drug efflux and reversal therapy of cancer, J. Bioenerg. Biomembr. 28:279–284.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., Yang, J., and Pardridge, W. M., 1997, Drug targeting of a peptide radiopharmaceutical through the primate blood-brain barrier in vivo with a monoclonal antibody to the human insulin receptor, J. Clin. Invest. 100:1804–1812.

    PubMed  CAS  Google Scholar 

  • Yamazaki, M., Fukuoka, H., Nagata, O., Kato, H., Ito, Y., Terasaki, T., and Tsjui, A., 1994, Transport mechanism of an H1-antagonist at the blood-brain barrier: Transport mechanism of mepyramine using the carotid injection technique, Biol. Pharmaceut. Bull. 17:676–679.

    CAS  Google Scholar 

  • Zerangue, N., and Kavanaugh, M. P., 1996, Interaction of l-cysteine with a human excitatory amino acid transporter, J. Physiol. 493:419–423.

    PubMed  CAS  Google Scholar 

  • Zlokovic, B. V., Lipovac, M. N., Begley, D. J., Davson, H., and Rakic, L. J., 1987, Transport of leucine-enkephalin across the blood-brain barrier in the perfused guinea pig brain, J. Neurochem. 49:300–305.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic Publishers

About this chapter

Cite this chapter

Rochat, B., Audus, K.L. (2002). Drug Disposition and Targeting. In: Amidon, G.L., Sadée, W. (eds) Membrane Transporters as Drug Targets. Pharmaceutical Biotechnology, vol 12. Springer, Boston, MA. https://doi.org/10.1007/0-306-46812-3_6

Download citation

  • DOI: https://doi.org/10.1007/0-306-46812-3_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46094-4

  • Online ISBN: 978-0-306-46812-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics