Learning about kainate receptors

Abstract

Three classes of ionotropic glutamate receptors have been identified: NMDA (N-methyl-d-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate (KA) receptors 1 Watkins J.C. Evans R.H. Excitatory amino acid transmitters. Annu. Rev. Pharmacol. Toxicol. 1981; 21: 165-204 Crossref PubMed Scopus (1963) Google Scholar . The roles of AMPA and NMDA receptors in mediating fast synaptic transmission and synaptic plasticity, respectively, are well understood; however, the physiological function of the KA receptor family (comprising GluR5–7 and KA1–2 subunits) has remained obscure. This situation has stemmed primarily from the lack of selective pharmacological reagents. A consortium of academic and pharmaceutical laboratories, led by Graham Collingridge’s group at the University of Bristol (Bristol, UK) and a group at Eli Lilly in Indianapolis (IN, USA) headed by David Lodge and David Bleakman, has now provided the first evidence for a selective KA receptor antagonist 2 Bortolotto Z.A. et al. Kainate receptors are involved in synaptic plasticity. Nature. 1999; 402: 297-301 Crossref PubMed Scopus (271) Google Scholar . Both in expression systems and at native receptors, the compound LY382884 exhibits potent selective antagonism at KA receptors that contain the GluR5 subunit. Bortolotto et al. have used this powerful new pharmacological tool to explore the role of KA receptors in synaptic plasticity in the mossy fibre projection of the hippocampal formation. 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine (3s, 4ar, 6s, 8ar)-6-((4-carboxyphenyl) methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid)