title: A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission.
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 (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 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.
authors.affiliation: Department of Anatomy, University of Bristol, UK.
authors.forename: V R
authors.initials: VR
authors.lastname: Clarke
authors.forename: B A
authors.initials: BA
authors.lastname: Ballyk
authors.forename: K H
authors.initials: KH
authors.lastname: Hoo
authors.forename: A
authors.initials: A
authors.lastname: Mandelzys
authors.forename: A
authors.initials: A
authors.lastname: Pellizzari
authors.forename: C P
authors.initials: CP
authors.lastname: Bath
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: E F
authors.initials: EF
authors.lastname: Sharpe
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: P L
authors.initials: PL
authors.lastname: Ornstein
authors.forename: D D
authors.initials: DD
authors.lastname: Schoepp
authors.forename: R K
authors.initials: RK
authors.lastname: Kamboj
authors.forename: G L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: D
authors.initials: D
authors.lastname: Lodge
authors.forename: D
authors.initials: D
authors.lastname: Bleakman
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D007546:Isoquinolines; D007555:Isoxazoles; D007608:Kainic Acid; D011422:Propionates; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D013777:Tetrazoles; C108631:LY 294486; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate