Publication Details (including relevant citation information):
Clarke, Vernon R. J., Ballyk, Barbara A., Hoo, Ken H., Mandelzys, Allan, Pellizzari, Andrew, Bath, Catherine P., Thomas, Justyn, Sharpe, Erica F., Davies, Ceri H., Ornstein, Paul L., Schoepp, Darryle D., Kamboj, Rajender K., Collingridge, Graham L., Lodge, David, Bleakman, David Nature (London) 1997 389 (6651) 599-603
Abstract: The principal excitatory neurotransmitter in the vertebrate central nervous system, L-glutamate, acts on three classes of inotropic glutamate receptors, named after the agonists AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid), NMDA (N-methyl-D-aspartate) and kainate. The development of selective pharmacological agents has led to a detailed understanding of the physiological and pathological roles of AMPA and NMDA receptors. In contrast, the lack of selective kainate receptor ligands has greatly hindered progress in understanding the roles of kainate receptors. Here we describe the effects of a potent and selective agonist, ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic add) and a selective antagonist, LY294486 ((3SR, 4aRS, 6SR, 8aRS)-6-((((1H-tetrazol-5-yl) methyl)oxy)methyl)-1, 2,3,4,4a, 5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid), of the GluR5 subtype of kainate receptor. We have used these agents to show that kainate receptors, comprised of or containing GluR5 subunits, regulate synaptic inhibition in the hippocampus, an action that could contribute to the epileptogenic effects of kainate.