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

We have investigated the binding properties of [H-3]quisqualate to rat meta botropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain se ctions. Saturation isotherms gave K-D values of 27 +/- 4 and 81 +/- 22 nM f or mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited t he binding to mGlu1a and mGlu5a receptors concentration-dependently. (S)-4- Carboxyphenylglycine, (S)-4-carboxy-3-hydroxyphenylglycine, and (R,S)-1-ami noindan-1,5-dicarboxylic acid, which completely inhibited [H-3]quisqualate binding to the mGlu5a receptor, were inactive in a functional assay using t his receptor. The distribution and abundance of binding sites in rat and hu man brain sections were studied by quantitative receptor radioautography an d image analysis. Using 10 nM [H-3]quisqualate, a high density of binding w as detected in various brain regions with the following rank order of incre asing levels: medulla, thalamus, olfactory bulb, cerebral cortex, spinal co rd dorsal horn, olfactory tubercle, dentate gyrus molecular layer, CA1-3 or iens layer of hippocampus, striatum, and cerebellar molecular layer. The io notropic component of this binding could be inhibited by 30 muM kainate, re vealing the distribution of mGlu1+5 receptors. The latter were almost compl etely inhibited by the group I agonist (S)-3,5-dihydroxyphenylglycine. The binding profile correlated well with the cellular sites of synthesis and re gional expression of the respective group I receptor proteins revealed by i n situ hybridization histochemistry and immunohistochemistry, respectively.