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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen DH, Baker GJ (1981) N Engl J Med 305: 1154–1155
Biscoe TJ, Evans RH, Headley PM, Martin M, Watkins JC (1975) Nature 255: 166–167
Choi DW (1988) Neuron 1: 623–634
Collingridge GL, Lester RAJ (1989) Pharmacol Rev 41: 143–210
Daigo K (1959) J Pharmacol Soc Japan (Yakugakuzashi) 79: 353–356
Favaron M, Manev H, Alho H, Bertolino M, Ferret B, Guidotti A, Costa E (1988) Proc Natl Acad Sci U.S.A. 85: 7351–7355
Felbeck H, Wiley S (1987) Ref Biol Bull 173: 252–259
Gallo V, Giovannini C, Levi G (1989) J Neurochem 52: 10–16
Glavin GB, Pinsky C, Bose R (1989) TiPS 10: 15–16
Hill DW, Walters FH, Wilson TD, Stuart JD (1979) Anal Chem 51: 1338–1341
Hoyaux J, Gilles R, Jeuniaux CH (1976) Comp Biochem Physiol 53 A: 361–365
Livingstone DR, Widdows J, Fieth P (1979) Mar Biol 53: 41–55
Maeda M, Kodama T, Tanaka T, Ohfune Y, Nomoto K, Ishimura K, Fujita T (1984) J Pestic Sci 9: 27–32
McCaslin PP, Morgan WW (1987) Brain Res 417: 380–384
McCaslin PP, Smith TG (1988) Eur J Pharmacol 152: 341–346
Nicoletti F, Wroblewsky JT, Novelli A, Alho H, Guidotti A, Costa E (1986) J Neurosci 6: 1905–1911
Novelli A, Henneberry RC (1987 a) Dev Brain Res 34: 307–310
Novelli A, Nicoletti F, Wroblewski JT, Alho H, Costa E, Guidotti A (1987 b) J Neurosci 7: 40–47
Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Brain Res 451: 205–212
Novelli A, Kispert J, Reilly A, Zitko V (1990) Can Dis Wkly Rep 16 S1E: 83–89
Olney JW (1969) Science 164: 719–721
Olney JW, Zorumski C, Price MT, Labruyere J (1990) Science 248: 596–599
Perl TM, Bédard L, Kosatsky T, Hockin JC, Todd ECD, Remis RS (1990) N Engl J Med 322: 1775–1780
Schaumburg HH, Byck R, Gerstyle R, Masham JH (1969) Science 163: 826–828
Schousboe A, Drejer J, Hansen GH, Meier E (1985) Dev Neurosci 7: 252–262
Shumway SE, Gabbott PA (1977) J Exp Mar Biol Ecol 29: 131–150
Skurray GR, Pucar N (1988) Food Chem 27: 177–180
Stevens CF (1986) Nature 322: 210–211
Tasker RAR, Connell BJ, Strain SM (1991) Can J Physiol Pharm (in press)
Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, Cashman NR (1990) N Engl J Med 322: 1781–1787
Wood PL, Richard JW, Pilapil C, Nair NPV (1982) Neuropharmacology 21: 1235–1238
Wright JLC, Bird CJ, de Freitas ASW, Hampson D, Mc Donald J, Quilliam MA (1990) Can Dis Wkly Rep 16 S1E: 21–26
Zaczek R, Coyle JT (1982) Neuropharmacology 21: 15–26
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Novelli, A., Fernández-Sánchez, M.T., Kispert, J. et al. The amnesic shellfish poison domoic acid enhances neurotoxicity by excitatory amino acids in cultured neurons. Amino Acids 2, 233–244 (1992). https://doi.org/10.1007/BF00805945
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00805945