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Characterization of [ 3 H]Quisqualate Binding to Recombinant Rat Metabotropic Glutamate 1a and 5a Receptors and to Rat and Human Brain Sections
Author(s) -
Mutel Vincent,
Ellis Gareth J.,
Adam Geo,
Chaboz Sylvie,
Nilly Agnes,
Messer Jürg,
Bleuel Zaiga,
Metzler Veit,
Malherbe Pari,
Schlaeger ErnstJürgen,
Roughley Brian S.,
Faull Richard L. M.,
Richards J. Grayson
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752590.x
Subject(s) - kainate receptor , metabotropic receptor , olfactory bulb , receptor , biology , ionotropic effect , metabotropic glutamate receptor , glutamate receptor , medicine , microbiology and biotechnology , ionotropic glutamate receptor , biochemistry , endocrinology , biophysics , chemistry , central nervous system , ampa receptor
We have investigated the binding properties of[ 3 H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5areceptors and to rat and human brain sections. Saturation isotherms gave K D values of 27 ± 4 and 81 ± 22 n M for mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited thebinding 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 afunctional assay using this receptor. The distribution and abundance ofbinding sites in rat and human brain sections were studied by quantitativereceptor radioautography and image analysis. Using 10 n M [ 3 H]quisqualate, a high density of binding was detected in variousbrain regions with the following rank order of increasing levels: medulla,thalamus, olfactory bulb, cerebral cortex, spinal cord dorsal horn, olfactorytubercle, dentate gyrus molecular layer, CA1‐3 oriens layer of hippocampus,striatum, and cerebellar molecular layer. The ionotropic component of thisbinding could be inhibited by 30 μ M kainate, revealing thedistribution of mGlu1+5 receptors. The latter were almost completely inhibitedby the group I agonist ( S )‐3,5‐dihydroxyphenylglycine. The bindingprofile correlated well with the cellular sites of synthesis and regionalexpression of the respective group I receptor proteins revealed by in situhybridization histochemistry and immunohistochemistry, respectively.