Domoic acid induces neurotoxicity and ip3 mobilization in cultured cells of embryonic chick retina.
Domoic acid (DOM), 1 to 50 microM, a glutamate agonist responsible for several neurological effects such as loss of memory and confusion, induced the death of cultured neurons of chick embryonic retina, in a concentration- and Ca(2+)-dependent manner. This effect was blocked by 100 microM CNQX, a competitive antagonist of the non-NMDA receptor, but not by 10 microM MK-801, a non-competitive antagonist of the NMDA receptor. DOM also induced inositol triphosphate (ip3) accumulation 4 to 7 times above basal levels. This effect was also dependent on external Ca2+ and was entirely blocked by 100 microM CNQX, but not by 10 microM MK-801. These results suggest that DOM interaction with non-NMDA glutamate receptors mediates signal transduction with ip3 accumulation and cell death.
Duran
R
R
Laboratório de Neuroquímica, Universidade Federal do Rio de Janeiro, Brasil.
Reis
R A
RA
Almeida
O M
OM
de-Mello
M C
MC
de-Mello
F G
FG
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D007294:Inositol / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012160:Retina / Q000166:cytology* / Q000187:drug effects
D002118:Calcium; D007294:Inositol; D007608:Kainic Acid; D009498:Neurotoxins; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C012301:domoic acid