Direct Evidence That Excitotoxicity in Cultured Neurons Is Mediated via N ‐Methyl‐D‐Aspartate (NMDA) as well as Non‐NMDA Receptors

Direct Evidence That Excitotoxicity in Cultured Neurons Is Mediated via N... Abstract: Cultured GABAergic cerebral cortex neurons were exposed to the excitatory amino acid (EAA) L‐glutamate, kainate (KA), N‐methyl‐D‐aspartate (NMDA), or RS‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolopropionate (AMPA). To ensure a constant glutamate concentration in the culture media during the exposure periods, the glutamate uptake inhibitor L‐aspartic acid β‐hydroxamate was added at 500 μM to the cultures that were exposed to glutamate. Each of these EAAs was able to induce neurotoxicity. It was not possible to reduce or prevent glutamate‐induced cytotoxicity by blocking only one of the glutamate receptor subtpes with either the NMDA receptor antagonist D‐(‐)‐2‐amino‐5‐phosphonopentanoate (APV) or with one of the specific non‐NMDA antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX). However, if the cultures were exposed simultaneously to glutamate and the antagonists in combination, i.e., APV plus CNQX or APV plus DNQX, the toxicity was completely prevented. Furthermore, CNQX and DNQX were shown to be selective blockers of cytotoxic phenomena induced by non‐NMDA glutamate agonists with no effect on NMDA‐induced cell death. Likewise, APV prevented NMDA‐induced cell death without affecting the KA‐ or AMPA‐induced neurotoxicity. It is concluded that EAA‐dependent neurotoxicity is induced by NMDA as well as non‐NMDA receptors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Direct Evidence That Excitotoxicity in Cultured Neurons Is Mediated via N ‐Methyl‐D‐Aspartate (NMDA) as well as Non‐NMDA Receptors

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Publisher
Wiley
Copyright
Copyright © 1989 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1989.tb07327.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: Cultured GABAergic cerebral cortex neurons were exposed to the excitatory amino acid (EAA) L‐glutamate, kainate (KA), N‐methyl‐D‐aspartate (NMDA), or RS‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolopropionate (AMPA). To ensure a constant glutamate concentration in the culture media during the exposure periods, the glutamate uptake inhibitor L‐aspartic acid β‐hydroxamate was added at 500 μM to the cultures that were exposed to glutamate. Each of these EAAs was able to induce neurotoxicity. It was not possible to reduce or prevent glutamate‐induced cytotoxicity by blocking only one of the glutamate receptor subtpes with either the NMDA receptor antagonist D‐(‐)‐2‐amino‐5‐phosphonopentanoate (APV) or with one of the specific non‐NMDA antagonists 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX). However, if the cultures were exposed simultaneously to glutamate and the antagonists in combination, i.e., APV plus CNQX or APV plus DNQX, the toxicity was completely prevented. Furthermore, CNQX and DNQX were shown to be selective blockers of cytotoxic phenomena induced by non‐NMDA glutamate agonists with no effect on NMDA‐induced cell death. Likewise, APV prevented NMDA‐induced cell death without affecting the KA‐ or AMPA‐induced neurotoxicity. It is concluded that EAA‐dependent neurotoxicity is induced by NMDA as well as non‐NMDA receptors.

Journal

Journal of NeurochemistryWiley

Published: Jul 1, 1989

References

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