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

Neurotoxic profiles of putative agonists for low-affinity kainate subtypes of L-glutamate receptors (GluR5-7) were determined in cultured cortical neu rones. Rank order of neurotoxic potency (mu M): (S)-5-iodowillardiine (9) a pproximate to (2 S,4 R,6 E)-2-amino-4-carboxy-7 -(2-naphthyl)hept-6-enoic a cid (LY339434, 11) > (2S,4R)-4-methylglutamate (33) > kainate (100) > (RS)- 2-amino-3-(hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA, 360). Us ing ionotropic glutamate receptor antagonists, neurotoxicity induced by kai nate, ATPA and (S)-5-iodowillardiine appeared to involve a GluR5-7 componen t, unlike LY339434 and (2 S,4R)-4-methylglutamate. These putative GluR5-7 a gonists exhibited complex excitotoxic profiles highlighting the importance of studying native glutamate receptors. (C) 1999 Elsevier Science B.V. All rights reserved.