title: New developments in the molecular pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainate receptors.
abstract: Separation of non-N-methyl-D-aspartate subtypes of glutamate receptors, known as alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors, is traced through conventional pharmacology to molecular biology. The physiology and pharmacology of recombinant receptor subtypes (GluR1-7 and KA1-2) are described. Competitive antagonists, e.g., the quinoxalinedione, 2,3-dihyroxy-6-nitro-7-sulphamoyl-benz(F)quinoxaline, and the decahydroisoquinoline, 3S,4aR,6R, 8aR-6-[2-(1(2)H-tetrazol-5-yl)ethyl]-decahydroisoquinolin e-3-carboxylate, have a broad antagonist spectrum, except that the latter is inactive on GluR6. The 2,3-benzodiazepines noncompetitively antagonise the AMPA receptor GluR1-4. Desensitisation of AMPA (GluR1-4) and kainate (GluR5-7 and KA1-2) receptors is blocked by cyclothiazide and concanavalin A, respectively. Polyamine toxins block AMPA receptors not containing GluR2 and unedited kainate receptors (GluR5-6). These data correlate well with results on native neurons characterised by techniques such as in situ hybridisation.
authors.affiliation: MRC Laboratory of Molecular Biology/Department of Zoology, Cambridge, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Fletcher
authors.forename: D
authors.initials: D
authors.lastname: Lodge
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D017398:Alternative Splicing; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017403:In Situ Hybridization; D007473:Ion Channels / Q000037:antagonists & inhibitors; D009865:Oocytes / Q000166:cytology / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000145:classification; D018092:Kainic Acid Receptors / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001569:Benzodiazepines; D018690:Excitatory Amino Acid Agonists; D007473:Ion Channels; D011804:Quinolines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid