Quisqualate neurotoxicity: a delayed, CNQX-sensitive process triggered by a CNQX-insensitive mechanism in young rat hippocampal slices.
Exposure of slices of young rat hippocampus for 30 min to the glutamate receptor agonist, quisqualate (QA, 30 microM), led, after a 90 min recovery period, to severe 'dark cell degeneration' of pyramidal neurones, most extensively those in CA3. When present during the exposure, 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM), an antagonist with preferential action on non-N-methyl-D-aspartate receptors, did not prevent this toxic effect of QA. However, it was effective when included either during the recovery period as well or, indeed, only during recovery. Comparable results were obtained with kynurenate (3 mM), but not with D,L-2-amino-5-phosphonovalerate (100 microM) or with tetrodotoxin (0.5 microM). Grease-gap recordings showed that CNQX markedly inhibited QA-induced depolarization. It is concluded that QA toxicity is not triggered by QA-induced depolarization but instead involves CNQX-resistant QA receptors, possibly those linked to phospholipid metabolism. The induction mechanism does not itself cause irreversible injury but subsequently, a delayed form of damage takes place which is mediated by activation of CNQX/kynurenate-sensitive receptors.
Garthwaite
G
G
Department of Physiology, University of Liverpool, U.K.
Garthwaite
J
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology / Q000633:toxicity*; D011810:Quinoxalines / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D010069:Oxadiazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; D007736:Kynurenic Acid