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Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors

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Abstract

Kainic acid (KA), a conformationally restricted analogue of glutamic acid, exhibits potent neuroexcitatory1 and neurotoxic properties2. The mechanism of the neurotoxicity of KA, however, seems to be complex and indirect because in many brain areas neuronal vulnerability requires the integrity of excitatory afferents3–6. Nevertheless, neurophysiological studies indicate that the neuroexcitatory effects of KA in the mammalian brain are direct7. We have now examined the effects of KA and other excitatory amino acids on the stimulation of cyclic GMP formation in brain slices incubated in vitro as a method for monitoring their depolarizing effects8. We show in the adult mouse cerebellum that the excitatory amino acid antagonist, D-α-aminoadipate (DAA)9, blocks the stimulation of cyclic GMP produced by N-methyl-D,L-aspartate (NMDLA) but potentiates the effects of KA. Whereas KA causes a significant release of both aspartic (Asp) and glutamic (Glu) acids by a calcium-dependent process, NMDLA is without effect; furthermore, the effects of KA on Glu release are markedly reduced in cerebellum deficient in granule cells. KA also releases Glu and Asp from hippocampal and striatal slices, indicating that this response is not unique to the cerebellum. The results are consistent with evidence that KA has direct excitatory effects on neurones7 but suggest that its potent neurotoxic action involves the activation of presynaptic receptors on glutamatergic and aspartergic terminals, thereby releasing Asp and Glu.

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References

  1. Biscoe, T. J., Evans, R. H., Headley, P. M., Martin, M. R. & Watkins, J. C. Br. J. Pharmac. 58, 373–382 (1976).

    Article  CAS  Google Scholar 

  2. Olney, J. W., Rhee, V. & Ho, O. L. Brain Res. 77, 507–512 (1974).

    Article  CAS  Google Scholar 

  3. Coyle, J. T. & Schwarcz, R. Nature 263, 244–246 (1976).

    Article  ADS  CAS  Google Scholar 

  4. McGeer, E. G., McGeer, P. L. & Singh, K. Brain Res. 139, 381–383 (1978).

    Article  CAS  Google Scholar 

  5. Biziere, K. & Coyle, J. T. Neurosci. Lett. 8, 303–310 (1978).

    Article  CAS  Google Scholar 

  6. Kohler, C., Schwarcz, R. & Fuze, K. Neurosci. Lett. 10, 241–24 (1978).

  7. McLennan, H. Neurosci. Lett. 18, 313–316 (1980).

    Article  CAS  Google Scholar 

  8. Foster, G. A. & Roberts, P. J. Life Sci. 27, 215–221 (1980).

    Article  CAS  Google Scholar 

  9. Watkins, J. C. & Evans, K. H. A. Rev. Pharmac. 21, 165–203 (1981).

    Article  CAS  Google Scholar 

  10. Slevin, J., Johnston, M. V., Biziere, K. & Coyle, J. T. Dev. Neurosci. 5, 3–12 (1982).

    Article  CAS  Google Scholar 

  11. Steiner, A. L., Ferrendelli, J. A. & Kipnis, R. M. J. biol. Chem. 247, 1121–1124 (1972).

    CAS  PubMed  Google Scholar 

  12. Nelson, M. F., Zaczek, R. & Coyle, J. T. J. Pharmac. exp. Ther. 214, 694–702 (1980).

    CAS  Google Scholar 

  13. Hill, P. W., Walters, F. H., Wilson, T. D. & Stuart, J. D. Analyt. Chem. 51, 1338–1341 (1979).

    Article  CAS  Google Scholar 

  14. Stone, T. W. Br. J. Pharmac. 66, 291–296 (1979).

    Article  CAS  Google Scholar 

  15. London, E. D. & Coyle, J. T. Molec. Pharmac. 15, 492–505 (1979).

    CAS  Google Scholar 

  16. Johnston, G. A. R., Kennedy, S. M. E. & Twitchin, B. J. Neurochem. 32, 121–127 (1979).

    Article  CAS  Google Scholar 

  17. Evans, R. H. J. Physiol., Lond. 298, 25–35 (1980).

    Article  CAS  Google Scholar 

  18. Young, A., Oster-Granite, M., Herndon, R. & Snyder, S. H. Brain Res. 73, 1–13 (1974).

    Article  CAS  Google Scholar 

  19. Sandoval, M. & Cotman, C. Neurosciences 3, 199–206 (1978).

    Article  CAS  Google Scholar 

  20. Wiklund, L., Toggenburger, G. & Cuenod, M. Science 216, 78–80 (1982).

    Article  ADS  CAS  Google Scholar 

  21. Nadi, N. S., Kanter, D., McBride, W. J. & Aprison, M. H. J. Neurochem. 28, 661–662 (1977).

    Article  CAS  Google Scholar 

  22. Foster, G. A. & Roberts, P. J. Neurosci. Lett. 23, 67–70 (1981).

    Article  CAS  Google Scholar 

  23. Nicklas, W., Krespan, B. & Berl, S. B. Eur. J. Pharmac. 62, 209–213 (1980).

    Article  CAS  Google Scholar 

  24. Retz, K. C. & Coyle, J. T. J. Neurochem. 38, 196–203 (1982).

    Article  CAS  Google Scholar 

  25. Davies, J., Evans, R. H., Francis, A. A. & Watkins, J. C. J. physiol., Paris 75, 641–654 (1979).

    CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Neuroscience, Pharmacology and Experimental Therapeutics, and Psychiatry and the Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, USA

    John W. Ferkany, Robert Zaczek & Joseph T. Coyle

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  1. John W. Ferkany
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  2. Robert Zaczek
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  3. Joseph T. Coyle
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Ferkany, J., Zaczek, R. & Coyle, J. Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298, 757–759 (1982). https://doi.org/10.1038/298757a0

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