Characterization of [[sup3]H]Quisqualate Binding to Recombinant Rat Metabotropic Glutamate 1a and 5a Receptors and to Rat and Human Brain Sections.

Autor: Mutel, Vincent, Ellis, Gareth J., Adam, Geo, Chaboz, Sylvie, Nilly, Agnes, Messer, Jürg, Bleuel, Zaiga, Metzler, Veit, Malherbe, Pari, Schlaeger, Ernst-Jürgen, Roughley, Brian S., Faull, Richard L.M., Richards, J. Grayson
Předmět:
Zdroj: Journal of Neurochemistry; Dec2000, Vol. 75 Issue 6, p2590, 12p, 12 Black and White Photographs, 4 Diagrams, 2 Charts, 7 Graphs
Abstrakt: Abstract: We have investigated the binding properties of [[sup3]H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain sections. Saturation isotherms gave K[subD] 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-hydroxyphenyl-glycine, and (R,S)-1-aminoindan-1,5-dicarboxylic acid, which completely inhibited [[sup3]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 [[sup3] H]quisqualate, a high density of bind-ing 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 bind-ing could be inhibited by 30 μM 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
Externí odkaz: