Quinolinate mimics neurotoxic actions of N-methyl-D-aspartate in rat cerebellar slices.
Incubation of slices of immature rat cerebellum for 30 min with quinolinate (QUIN), an endogenous neurotoxin, resulted in the selective necrosis of granule cells and intracerebellar nucleus neurones. Concentration of QUIN in the millimolar range were needed for these effects. The same neuronal populations were also selectively killed by N-methyl-D-aspartate (NMDA) but the toxic potency of NMDA was 40-fold higher than that of QUIN. Depolarizing responses of granule cells to brief applications of QUIN and NMDA were recorded using a gap method. Dose-response curves to the two compounds appeared parallel but NMDA was 30-fold more potent than QUIN. The depolarizing and toxic actions of QUIN and NMDA were inhibited by the NMDA antagonist, 2-amino-5-phosphonopentanoate. We conclude that the selective toxicity of QUIN in this tissue arises from its activity on NMDA receptors.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D016202:N-Methylaspartate; D009410:Nerve Degeneration / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats
D011725:Pyridines; D011805:Quinolinic Acids; D001224:Aspartic Acid; D016202:N-Methylaspartate; D017378:Quinolinic Acid