A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission

• Published in: Nature (London) 1997-10, Vol.389 (6651), p.599-603
• Main Authors: Bleakman, David, 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
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological and medical sciences; Brain; Carboxylic acids; Cell Line; Cellular biology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cloning, Molecular; Excitatory Amino Acid Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; Hippocampus - physiology; Humanities and Social Sciences; Humans; Isoquinolines - pharmacology; Isoxazoles - pharmacology; Kainic Acid - pharmacology; letter; multidisciplinary; Neural Inhibition - physiology; Neurons; Pharmacology; Propionates - pharmacology; Rats; Receptors, GABA-A - metabolism; Receptors, Kainic Acid - agonists; Receptors, Kainic Acid - antagonists & inhibitors; Receptors, Kainic Acid - physiology; Science; Science (multidisciplinary); Synapses - physiology; Tetrazoles - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/39315

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 ofthe 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 rolesof 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.