Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections

J Neurochem. 2000 Dec;75(6):2590-601. doi: 10.1046/j.1471-4159.2000.0752590.x.


We have investigated the binding properties of [(3)H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain sections. Saturation isotherms gave K:(D) values of 27 +/- 4 and 81 +/- 22 nM: for mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited the binding to mGlu1a and mGlu5a receptors concentration-dependently. (S:)-4-Carboxyphenylglycine, (S:)-4-carboxy-3-hydroxyphenylglycine, and (R,S)-1-aminoindan-1,5-dicarboxylic acid, which completely inhibited [(3)H]quisqualate binding to the mGlu5a receptor, were inactive in a functional assay using this receptor. The distribution and abundance of binding sites in rat and human brain sections were studied by quantitative receptor radioautography and image analysis. Using 10 nM: [(3)H]quisqualate, a high density of binding was detected in various brain regions with the following rank order of increasing levels: medulla, thalamus, olfactory bulb, cerebral cortex, spinal cord dorsal horn, olfactory tubercle, dentate gyrus molecular layer, CA1-3 oriens layer of hippocampus, striatum, and cerebellar molecular layer. The ionotropic component of this binding could be inhibited by 30 microM: kainate, revealing the distribution of mGlu1+5 receptors. The latter were almost completely inhibited by the group I agonist (S:)-3,5-dihydroxyphenylglycine. The binding profile correlated well with the cellular sites of synthesis and regional expression of the respective group I receptor proteins revealed by in situ hybridization histochemistry and immunohistochemistry, respectively.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / metabolism*
  • Calcium / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Indans / pharmacology
  • Intracellular Fluid / metabolism
  • Kainic Acid / pharmacology
  • Male
  • Organ Specificity
  • Quinazolines / pharmacology
  • Quisqualic Acid / pharmacokinetics*
  • Rats
  • Rats, Inbred Strains
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spinal Cord / metabolism
  • Transfection


  • 1-aminoindan-1,5-dicarboxylic acid
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Imidazoles
  • Indans
  • Quinazolines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Recombinant Proteins
  • Ro 48-8587
  • metabotropic glutamate receptor type 1
  • 4-carboxy-3-hydroxyphenylglycine
  • 4-hydroxyphenylglycine
  • Quisqualic Acid
  • Kainic Acid
  • Calcium
  • Glycine