Excitotoxic injury profiles of low-affinity kainate receptor agonists in cortical neuronal cultures

Abstract

Neurotoxic profiles of putative agonists for low-affinity kainate subtypes of L-glutamate receptors (GluR5-7) were determined in cultured cortical neurones. Rank order of neurotoxic potency (μM): (S)-5-iodowillardiine (9)~(2S,4R,6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434, 11)>(2S,4R)-4-methylglutamate (33)>kainate (100)>(RS)-2-amino-3-(hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA, 360). Using ionotropic glutamate receptor antagonists, neurotoxicity induced by kainate, ATPA and (S)-5-iodowillardiine appeared to involve a GluR5-7 component, unlike LY339434 and (2S,4R)-4-methylglutamate. These putative GluR5-7 agonists exhibited complex excitotoxic profiles highlighting the importance of studying native glutamate receptors. Copyright (C) 1999 Elsevier Science B.V.