A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission

Vernon R.J. Clarke, Barbara A. Ballyk, Ken H. Hoo, Allan Mandelzys, Andrew Pellizzari, Catherine P. Bath, Justyn Thomas, Erica F. Sharpe, Ceri H. Davies, Paul L. Ornstein, Darryle D. Schoepp, Rajender K. Kamboj, Graham L. Collingridge, David Lodge, David Bleakman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

384 Scopus citations


The principal excitatory neurotransmitter in the vertebrate central nervous system, L-glutamate, acts on three classes of ionotripic glutamate receptors, named after the agonists AMPA (α-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 acid) 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.

Original languageEnglish (US)
Pages (from-to)599-603
Number of pages5
Issue number6651
StatePublished - 1997

ASJC Scopus subject areas

  • General


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