The Basis for Active Transport at the Blood-Brain Barrier

  • A. L. Betz
  • G. W. Goldstein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 131)


Certain low molecular weight compounds have been shown to enter the brain by specific carrier-mediated transport systems in the endothelial cell membranes (1–4). At least eight such carriers capable of moving solutes from blood into brain have been described (4). Most of the blood-brain barrier (BBB) transport systems that have been described are not able to move solutes against concentration gradients, but instead, facilitate the equilibration of brain and blood concentrations for their particular substrates. Although the BBB acts as an impermeable wall for some solutes and a passive sieve for others, it is generally agreed that an important function is active regulation of the internal milieu of the central nervous system (CNS) (3,5,6). Several reports have suggested that the BBB can mediate solute efflux from the brain against a concentration gradient (7–13), but these studies utilized intact animals and, consequently, their interpretation is made difficult by the presence of neurons, glia and choroid plexus.


Active Transport Neutral Amino Acid Brain Capillary Brain Capillary Endothelial Cell Large Neutral Amino Acid 
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  1. 1.
    Betz AL, Gilboe DD, Drewes LR: The characteristics of glucose transport across the blood-brain barrier and its relation to cerebral glucose metabolism. In, Levi G, Battistin L, Lajtha A (eds): Transport phenomena in the Nervous System, New York, Plenum Press, 1976, pp 133–149.CrossRefGoogle Scholar
  2. 2.
    Lund-Andersen H: Transport of glucose from blood to brain. Physiol Rev 59: 305–352, 1979.PubMedGoogle Scholar
  3. 3.
    Oldendorf WH: The blood-brain barrier. Exp Eye Res 25 (Suppl): 177–190, 1977.CrossRefPubMedGoogle Scholar
  4. 4.
    Pardridge WM, Oldendorf WH: Transport of metabolic substrates through the blood-brain barrier. J Neurochem 28: 5–12, 1977.CrossRefPubMedGoogle Scholar
  5. 5.
    Davson H: The blood-brain barrier. J Physiol (Lond) 255: 1–28, 1976.CrossRefGoogle Scholar
  6. 6.
    Rapoport SI: Blood-brain Barrier in Physiology and Medicine. New York, Raven Press, 1976.Google Scholar
  7. 7.
    Bito LZ, Davson H, Hollingsworth J: Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and blood-brain barriers. J Physiol (Lond) 256: 273–285, 1976.CrossRefGoogle Scholar
  8. 8.
    Bradbury MWB, Segal MP, Wilson J: Transport of potassium at the blood-brain barrier. J Physiol (Lond) 221: 617–632, 1972.CrossRefGoogle Scholar
  9. 9.
    Davson H, Hollingsworth JR: Active transport 131I across the blood-brain barrier. J Physiol (Lond) 233: 327–347, 1973.CrossRefGoogle Scholar
  10. 10.
    Katzman R: Maintenance of a constant brain extracellular potassium. Fed Proc 35: 1244–1247, 1976.PubMedGoogle Scholar
  11. 11.
    Lajtha A, Toth J: The brain barrier system II. Uptake and transport of amino acids by the brain. J Neurochem 8: 216–225, 1961.CrossRefPubMedGoogle Scholar
  12. 12.
    Lorenzo AV, Snodgrass SR: Leucine transport from the ventricles and the cranial subarachnoid space in the cat. J Neurochem 19: 1287–1298, 1972.CrossRefPubMedGoogle Scholar
  13. 13.
    Murray JE, Cutler RWP: Transport of glycine from the cerebro spinal fluid. Factors regulating amino acid concentra-tion in feline cerebrospinal fluid. Arch Neurol 23: 23–31, 1970.CrossRefPubMedGoogle Scholar
  14. 14.
    Kotyk A, Janacek K: Cell Membrane Transport. Principles and Techniques, New York, Plenum Press, 1975, pp 139–158.CrossRefGoogle Scholar
  15. 15.
    Hopfer U, Sigrist-Nelson K, Ammann E, Murer H: Differences in neutral amino acid and glucose transport between brush border and basolateral plasma membrane of intestinal cells. J Cell Physiol 89: 805–810, 1976.CrossRefPubMedGoogle Scholar
  16. 16.
    Murer H, Kinne R: Sidedness and coupling of transport processes in small intestinal and renal epithelia. In, Semenza G, Carafoli E (eds): Biochemistry of Membrane Transport, New York, Springer-Verlag, 1977, pp 292–304.Google Scholar
  17. 17.
    Pisam M, Ripoche P: Redistribution of surface macromolecules in dissociated epithelial cells. J Cell Biol 71: 907–920, 1976.CrossRefPubMedGoogle Scholar
  18. 18.
    Staehelin LA, Hull BE: Junctions between living cells. Sci Am 238: 141–152, 1978.CrossRefGoogle Scholar
  19. 19.
    Brightman MW, Reese TS: Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40: 648–677, 1969.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Brightman MW, Reese TS, Feder N: Assessment with the Electron Microscope of the Permeability to Peroxidase of Cerebral Endothelium in Mice and Sharks. In, Crone C, Lassen NA (eds): Capillary Permeability, Proceedings of the Alfred Benzon Symposium II, New York, Academic Press, 1970, pp 463–476.Google Scholar
  21. 21.
    Reese TS, Karnovsky MJ: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34: 207–217, 1967.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Oldendorf WH, Cornford ME, Brown WJ: The large apparent work capability of the blood-brain barrier: A study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1: 409–417, 1977.CrossRefPubMedGoogle Scholar
  23. 23.
    Betz AL, Csejtey J, Goldstein GW: Hexose transport and phosphorylation by capillaries isolated from rat brain. Am J Physiol 236: C96–C102, 1979.PubMedGoogle Scholar
  24. 24.
    Betz AL, Goldstein GW: Polarity of the blood-brain barrier: Neutral amino acid transport into isolated brain capillaries. Science 202: 225–227, 1978.CrossRefPubMedGoogle Scholar
  25. 25.
    Hjelle JT, Baird-Lambert J, Cardinale G, Spector S, Udenfriend S: Isolated microvessels: The blood-brain barrier in vitro. Proc Natl Acad Sci 75: 4544–4548, 1978.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Sershen H, Lajtha A: Capillary transport of amino acids in the developing brain. Expl Neurol 53: 465–474, 1976.CrossRefGoogle Scholar
  27. 27.
    Christensen HN: On the development of amino acid transport systems. Fed Proc Fed Am Soc Exp Biol 32: 19–28, 1973.Google Scholar
  28. 28.
    Oldendorf WH: Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection. Am J Physiol 221: 1629–1639, 1971.PubMedGoogle Scholar
  29. 29.
    Pardridge WM: Kinetics of competitive inhibition of neutral amino acid transport across the blood-brain barrier. J Neurochem 28: 103–108, 1977.CrossRefPubMedGoogle Scholar
  30. 30.
    Wade LA, Katzman R: Synthetic amino acids and the nature of L-DOPA transport at the blood-brain barrier. J Neurochem 25: 837–842, 1975.CrossRefPubMedGoogle Scholar
  31. 31.
    Goldstein GW: Relation of potassium transport to oxidative metabolism in isolated brain capillaries. J Physiol (Lond) 286: 185–195, 1979.CrossRefGoogle Scholar
  32. 32.
    Betz AL, Firth JA, Goldstein GW: Polarity of the blood-brain barrier: Distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res (In press).Google Scholar
  33. 33.
    Samuels S, Fish I, Freedman LS: Effect of γ-glutamyl cycle inhibitors on brain amino acid transport and utilization. Neurochem Res 3: 619–631, 1978.CrossRefPubMedGoogle Scholar
  34. 34.
    Perry TL, Hansen S, Kennedy J: CSF amino acids and plasma-CSF amino acid ratios in adults. J Neurochem 24: 587–589, 1975.CrossRefPubMedGoogle Scholar
  35. 35.
    Bass NH, Lundberg P: Transport mechanisms in the cerebro spinal fluid system for removal of acid metabolites from developing brain. In, Levi G, Battistin L, Lajtha A (eds): Transport Phenomena in the Nervous System. New York, Plenum Press, 1976, pp 31–40.CrossRefGoogle Scholar
  36. 36.
    Milhorat TH, Hammock MK, Fenstermacher JD, Rail DP, Levin VA: Cerebrospinal fluid production by the choroid plexus and brain. Science 173: 330–332, 1971.CrossRefPubMedGoogle Scholar
  37. 37.
    Herbst TJ, Raichle ME, Ferrendelli JA: ß-adrenergic regula tion of adenosine 3′–5′–monophosphate concentration in brain microvessels. Science 204: 330–332, 1979.CrossRefPubMedGoogle Scholar
  38. 38.
    Nathanson JA, Glaser GH: Identification of ß-adrenergicsensitive adenylate cyclase in intracranial blood vessels. Nature 278: 567–569, 1979.CrossRefPubMedGoogle Scholar
  39. 39.
    Betz AL, Gilboe DD, Drewes LR: Kinetics of unidirectional leucine transport into brain: Effects of isoleucine, valine and anoxia. Am J Physiol 228: 895–900, 1975.PubMedGoogle Scholar
  40. 40.
    Oldendorf WH: Stereospecificity of blood-brain barrier permeability to amino acids. Am J Physiol 224: 967–969, 1973.PubMedGoogle Scholar
  41. 41.
    Yudilevich DL, De Rose N, Sepulveda FV: Facilitated transport of amino acids through the blood-brain barrier of dog studied in a single capillary circulation. Brain Res 44: 569–578, 1972.CrossRefPubMedGoogle Scholar
  42. 42.
    Hansen AJ, Lund-Andersen H, Crone C: K+-permeability of the blood-brain barrier, investigated by aid of a K+- sensitive microelectrode. Acta Physiol Scand 101: 438–445, 1977.CrossRefPubMedGoogle Scholar
  43. 43.
    Bito LZ, Bradbury MWB, Davson H: Factors affecting the distribution of iodide and bromide in the central nervous system. J Physiol (Lond) 185: 323–354, 1966.CrossRefGoogle Scholar
  44. 44.
    Oldendorf WH: Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am J Physiol 224:1450–1453, 1973.PubMedGoogle Scholar
  45. 45.
    Wagner HJ, Pilgrim C, Brandl J: Penetration and removal of horseradish peroxidase injected into the cerebrospinal fluid: Role of cerebral perivascular spaces, endothelium and microglia. Acta Neuropath (Berl) 27: 299–315, 1974.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • A. L. Betz
    • 1
    • 2
  • G. W. Goldstein
    • 1
    • 2
  1. 1.Department of Pediatrics, University HospitalUniversity of MichiganAnn ArborUSA
  2. 2.Department of Neurology, University HospitalUniversity of MichiganAnn ArborUSA

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