title: 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 (microM): (S)-5-iodowillardiine (9) approximately = (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.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: R X
authors.initials: RX
authors.lastname: Moldrich
authors.forename: N S
authors.initials: NS
authors.lastname: Cheung
authors.forename: C J
authors.initials: CJ
authors.lastname: Pascoe
authors.forename: P M
authors.initials: PM
authors.lastname: Beart
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian / Q000187:drug effects; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D051379:Mice; D017470:Receptors, Glutamate / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000819:agonists*
chemical_list: D018683:Excitatory Amino Acid Agents; D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors