New developments in the molecular pharmacology of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and kainate receptors

Pharmacol Ther. 1996;70(1):65-89. doi: 10.1016/0163-7258(96)00014-9.

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.

Publication types

  • Review

MeSH terms

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

Substances

  • Excitatory Amino Acid Agonists
  • Ion Channels
  • Quinolines
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Recombinant Proteins
  • Benzodiazepines
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid