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.
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