Paul Ornstein - A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission

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      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.

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