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 and David Bleakman
Additional contact information
Vernon R. J. Clarke: University of Bristol, University Walk
Barbara A. Ballyk: Allelix Biopharmaceuticals
Ken H. Hoo: Allelix Biopharmaceuticals
Allan Mandelzys: Allelix Biopharmaceuticals
Andrew Pellizzari: Allelix Biopharmaceuticals
Catherine P. Bath: Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor
Justyn Thomas: Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor
Erica F. Sharpe: Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor
Ceri H. Davies: University of Edinburgh
Paul L. Ornstein: Eli Lilly and Company Ltd, Lilly Corporate Centre
Darryle D. Schoepp: Eli Lilly and Company Ltd, Lilly Corporate Centre
Rajender K. Kamboj: Allelix Biopharmaceuticals
Graham L. Collingridge: University of Bristol, University Walk
David Lodge: Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor
David Bleakman: Eli Lilly and Company Ltd, Lilly Research Centre, Erl Wood Manor

Nature, 1997, vol. 389, issue 6651, 599-603

Abstract: Abstract 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 kainate1. The development of selective pharmacological agents has led to a detailed understanding ofthe physiological and pathological roles of AMPA and NMDA receptors2,3,4,5,6,7,8. In contrast, the lack of selective kainate receptor ligands has greatly hindered progress in understanding the rolesof kainate receptors9,10. 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 receptor11. 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 kainate12,13,14,15,16,17.

Date: 1997
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DOI: 10.1038/39315

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