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)≈(2 S,4 R,6 E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434, 11)>(2 S,4 R)-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 (2 S,4 R)-4-methylglutamate. These putative GluR5-7 agonists exhibited complex excitotoxic profiles highlighting the importance of studying native glutamate receptors.
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