Blood-Brain Barrier Permeability to Excitatory Amino Acids

  • J. M. Lefauconnier
  • Y. Tayarani
  • G. Bernard
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 203)


The blood-brain barrier is situated at the layer of endothelial cells of brain capillaries (Rapoport, 1976; Bradbury, 1979). These cells are connected together by tight junctions, which prevent significant paracellular diffusion, and they contain very few transfer vesicles. As a consequence of these characteristics, a blood-borne solute must successively pass through the two membranes (luminal and antiluminal) and the cytoplasm of the endothelial cells before reaching the brain extracellular space. Molecules pass through the membranes by passive diffusion as a function of the lipid solubility of their undissociated form and of the extent of their dissociation at physiological pH (only the undissociated form is able to traverse the membranes). Molecules like amino acids, which are dissociated at normal pH, are thus nearly excluded from blood-brain transport unless they are transported by a specific carrier mechanism. These specific carriers are not all symmetrically distributed on the two membranes. Carriers on the luminal membrane seem to function mainly as exchange systems, while some carriers on the antiluminal membrane can produce active transport (Goldstein and Betz, 1983). An additional regulation of the passage of solutes can be exerted by cytoplasmic enzymes which can catabolize metabolites which have entered the endothelial cytoplasm (Bertler et al., 1966).


Kainic Acid Glutamate Decarboxylase Luminal Membrane Brain Capillary Transfer Constant 
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  1. Ben-Ari, Y., 1985, Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy, Neuroscience 14: 375.Google Scholar
  2. Bertler, A., Falck, B., Owman, C., and Rosengren, E., 1966, The localization of monoaminergic blood-brain barrier mechanisms, Pharmacol. Rev. 18:369.Google Scholar
  3. Blasberg, R.G., Fenstermacher, J.D., and Patlak, C.S., 1983, TransportGoogle Scholar
  4. of a-aminoisobutyric acid across brain capillary and cellular membranes, J. Cereb. Blood Flow Metabol. 3:8.Google Scholar
  5. Bradbury, M., 1979, The Concept of a Blood-Brain Barrier Wiley and Sons, London.Google Scholar
  6. Christensen, H.N., and Makowske, M., 1983, Recognition chemistry of anionic amino acids for hepatocyte transport and for neurotransmittory action compared, Life Sci. 33: 2255.Google Scholar
  7. Foster, A.C., and Fagg, G.E., 1984, Acidic amino acid binding sites inGoogle Scholar
  8. mammalian neuronal membranes: their characteristics and relationship to synaptic receptors, Brain Res. Rev. 7:103.Google Scholar
  9. Goldstein, G.W., Wolinski, J.S., Csejtey, J., and Diamond, I., 1975, Isolation of metabolically active capillaries from the brain, J. Neurochem. 25:715.Google Scholar
  10. Goldstein, G.W., and Betz, A.L., 1983, Recent advances in understanding brain capillary function, Ann. Neurol. 14:389.Google Scholar
  11. Hardebo, J.E., and Owman, C., 1980, Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood-brain interface, Ann. Neurol. 8: 1.PubMedCrossRefGoogle Scholar
  12. Hutchinson, H.T., Eisenberg, H.M., and Haber, B., 1985, High-affinity transport of glutamate in rat brain microvessels, Exp. Neurol. 87:260.Google Scholar
  13. Joó, F., 1985, The blood-brain barrier in vitro: ten years of research on microvessels isolated from the brain, Neurochem. Int. 7:1.Google Scholar
  14. Lajtha, A., Berl, S., and Waelsch, H., 1959, Amino acid and protein metabolism of the brain - IV - The metabolism of glutamic acid, J. Neurochem. 3:322.Google Scholar
  15. Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J., 1951, Protein measurement with the Folin phenol reagent, J. Biol, Chem. 193:265.Google Scholar
  16. Mrsulja, B.B., and Djuricié, B.M., 1980, Biochemical characteristics of cerebral capillaries, in: The Cerebral Microvasculature H.M. Eisenberg and R.L. Suddith,Plenum Press, New York, p. 29.Google Scholar
  17. Ohno, K., Pettigrew, K.D., and Rapoport, S.I., 1978, Lower limit of cerebro-vascular permeability to non electrolytes in the conscious rat, Am. J. Physiol. 235:H299.Google Scholar
  18. Oldendorf, W.H., and Szabo, J., 1976, Amino acid assignment to one of three blood-brain amino acid carriers, Am. J. Physiol. 230:94.Google Scholar
  19. Patlak, C.S., Blasberg, R.G., and Fenstermacher, J.D., 1983, Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data, J. Cereb. Blood Flow Metabol. 3:1.Google Scholar
  20. Rapoport, S.I., 1976, Blood-Brain Barrier in Physiology and Medicine Raven Press, New York.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • J. M. Lefauconnier
    • 1
  • Y. Tayarani
    • 1
  • G. Bernard
    • 1
  1. 1.INSERM U 26ParisFrance

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