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.
MeSH terms
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Allosteric Regulation / drug effects
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Alternative Splicing
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Animals
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Benzodiazepines / metabolism
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Benzodiazepines / pharmacology
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Binding, Competitive
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Excitatory Amino Acid Agonists / chemistry
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Excitatory Amino Acid Agonists / metabolism
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Excitatory Amino Acid Agonists / pharmacology*
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Humans
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In Situ Hybridization
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Ion Channels / antagonists & inhibitors
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Oocytes / cytology
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Oocytes / drug effects
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Quinolines / chemistry*
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Quinolines / metabolism
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Quinolines / pharmacology
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Receptors, AMPA / antagonists & inhibitors*
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Receptors, AMPA / classification
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Receptors, Kainic Acid / classification
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Receptors, Kainic Acid / drug effects
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Receptors, Kainic Acid / metabolism*
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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Recombinant Proteins / pharmacology
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Xenopus laevis
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / chemistry
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*
Substances
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Excitatory Amino Acid Agonists
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Ion Channels
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Quinolines
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Receptors, AMPA
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Receptors, Kainic Acid
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Receptors, N-Methyl-D-Aspartate
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Recombinant Proteins
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Benzodiazepines
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid