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Amino Acids

, Volume 2, Issue 3, pp 233–244 | Cite as

The amnesic shellfish poison domoic acid enhances neurotoxicity by excitatory amino acids in cultured neurons

  • A. Novelli
  • M. T. Fernández-Sánchez
  • J. Kispert
  • A. Torreblanca
  • S. Gascón
  • V. Zitko
Article
  • 29 Downloads

Summary

A recent episode of human intoxication by cultured mussels containing a rare excitatory amino acid named domoic acid, received particular attention for its neurological implications. The intoxication produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times. Neuronal damage was found in the hippocampus and amygdala of four patients. We now report that in neuronal cultures the neurotoxicity of a domoic acid-containing mussel extract is the result of domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high amounts in mussel tissue. Moreover, we show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity. We present evidence suggesting that the neurotoxic synergism may be due to a reduction of Mg+ + block at the NMDA receptor-associated channel, following activation of NON-NMDA receptors by domoic acid.

Keywords

Amino acids Domoic acid Toxic mussels Toxic synergism Excitatory amino acids Biotoxins Environmental neurotoxins 

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References

  1. Allen DH, Baker GJ (1981) N Engl J Med 305: 1154–1155Google Scholar
  2. Biscoe TJ, Evans RH, Headley PM, Martin M, Watkins JC (1975) Nature 255: 166–167Google Scholar
  3. Choi DW (1988) Neuron 1: 623–634Google Scholar
  4. Collingridge GL, Lester RAJ (1989) Pharmacol Rev 41: 143–210Google Scholar
  5. Daigo K (1959) J Pharmacol Soc Japan (Yakugakuzashi) 79: 353–356Google Scholar
  6. Favaron M, Manev H, Alho H, Bertolino M, Ferret B, Guidotti A, Costa E (1988) Proc Natl Acad Sci U.S.A. 85: 7351–7355Google Scholar
  7. Felbeck H, Wiley S (1987) Ref Biol Bull 173: 252–259Google Scholar
  8. Gallo V, Giovannini C, Levi G (1989) J Neurochem 52: 10–16Google Scholar
  9. Glavin GB, Pinsky C, Bose R (1989) TiPS 10: 15–16Google Scholar
  10. Hill DW, Walters FH, Wilson TD, Stuart JD (1979) Anal Chem 51: 1338–1341Google Scholar
  11. Hoyaux J, Gilles R, Jeuniaux CH (1976) Comp Biochem Physiol 53 A: 361–365Google Scholar
  12. Livingstone DR, Widdows J, Fieth P (1979) Mar Biol 53: 41–55Google Scholar
  13. Maeda M, Kodama T, Tanaka T, Ohfune Y, Nomoto K, Ishimura K, Fujita T (1984) J Pestic Sci 9: 27–32Google Scholar
  14. McCaslin PP, Morgan WW (1987) Brain Res 417: 380–384Google Scholar
  15. McCaslin PP, Smith TG (1988) Eur J Pharmacol 152: 341–346Google Scholar
  16. Nicoletti F, Wroblewsky JT, Novelli A, Alho H, Guidotti A, Costa E (1986) J Neurosci 6: 1905–1911Google Scholar
  17. Novelli A, Henneberry RC (1987 a) Dev Brain Res 34: 307–310Google Scholar
  18. Novelli A, Nicoletti F, Wroblewski JT, Alho H, Costa E, Guidotti A (1987 b) J Neurosci 7: 40–47Google Scholar
  19. Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Brain Res 451: 205–212Google Scholar
  20. Novelli A, Kispert J, Reilly A, Zitko V (1990) Can Dis Wkly Rep 16 S1E: 83–89Google Scholar
  21. Olney JW (1969) Science 164: 719–721Google Scholar
  22. Olney JW, Zorumski C, Price MT, Labruyere J (1990) Science 248: 596–599Google Scholar
  23. Perl TM, Bédard L, Kosatsky T, Hockin JC, Todd ECD, Remis RS (1990) N Engl J Med 322: 1775–1780Google Scholar
  24. Schaumburg HH, Byck R, Gerstyle R, Masham JH (1969) Science 163: 826–828Google Scholar
  25. Schousboe A, Drejer J, Hansen GH, Meier E (1985) Dev Neurosci 7: 252–262Google Scholar
  26. Shumway SE, Gabbott PA (1977) J Exp Mar Biol Ecol 29: 131–150Google Scholar
  27. Skurray GR, Pucar N (1988) Food Chem 27: 177–180Google Scholar
  28. Stevens CF (1986) Nature 322: 210–211Google Scholar
  29. Tasker RAR, Connell BJ, Strain SM (1991) Can J Physiol Pharm (in press)Google Scholar
  30. Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman NR (1990) N Engl J Med 322: 1781–1787Google Scholar
  31. Wood PL, Richard JW, Pilapil C, Nair NPV (1982) Neuropharmacology 21: 1235–1238Google Scholar
  32. Wright JLC, Bird CJ, de Freitas ASW, Hampson D, Mc Donald J, Quilliam MA (1990) Can Dis Wkly Rep 16 S1E: 21–26Google Scholar
  33. Zaczek R, Coyle JT (1982) Neuropharmacology 21: 15–26Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. Novelli
    • 1
    • 2
  • M. T. Fernández-Sánchez
    • 1
  • J. Kispert
    • 2
  • A. Torreblanca
    • 1
  • S. Gascón
    • 1
  • V. Zitko
    • 3
  1. 1.Departamento de Biologia Funcional, Area de Bioquímica y Biología MolecularFacultad de Medicina, Universidad de OviedoOviedoEspaña
  2. 2.Laboratory of Molecular Biology, National Institute of Neurological Diseases and StrokeNational Institutes of HealthBethesdaUSA
  3. 3.Marine Chemical DivisionBiological StationSt. AndrewsCanada

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