Two components in neurotoxicity by L-2-amino-3-phosphonopropionate in cultured cerebellar neurons.
Exposure of cultured cerebellar neurons to the putative metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate (L-AP3) for 24 h produced a neurotoxic effect which was prevented by the addition of the NMDA receptor antagonist (+)-10,11-dihydro-5-methyl-5-H-dibenzo-[a,d]-cyclohepten-5,1 0-imine hydrogen maleate (MK-801). MK-801 did also reduce neurotoxicity following 72 h exposure to L-AP3 neurotoxicity in the presence of MK-801 was antagonized by glutamate. Our results suggest that metabotropic glutamate receptors may play an important role in neuronal survival by controlling NMDA receptor-dependent as well as independent pathways.
Novelli
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Departamento de Bioogia Funcional, Facultad de Medicina, Universidad de Oviedo, Spain.
Torreblanca
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Fernández-Sánchez
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C000211:2-amino-3-phosphonopropionic acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000409:Alanine