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Regional Distribution of α ‐[ 3 H]Amino‐3‐Hydroxy‐5‐Methylisoxazole‐4‐Propionic Acid Binding Sites in Rat Brain: Effect of Chemical Modification of SH– Groups in Tissue Sections
Author(s) -
Baudry Michel,
Monaghan Daniel,
Cotman Carl,
Altar C. Anthony
Publication year - 1990
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 - 10.1111/j.1471-4159.1990.tb01222.x
Subject(s) - ampa receptor , thiocyanate , chemistry , binding site , potassium thiocyanate , ligand (biochemistry) , biochemistry , amino acid , glutamate receptor , receptor , biophysics , stereochemistry , biology , inorganic chemistry
Previous studies have shown that chemical modifications of sulfhydryl (SH–) groups with mercurial compounds in rat brain membrane preparations increase the binding of α ‐[ 3 H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid ([ 3 H]AMPA), a ligand for the quisqualate/AMPA type of glutamate receptors. In the present study we investigated the regional distribution of SH– group modification by quantitative analysis of autoradiographic images of [ 3 H]AMPA binding in tissue sections. We also compared the effect of SH– group modification to that of the chaotropic ion thiocyanate (SCN − ) which has been generally utilized to study [ 3 H]AMPA binding sites. Low levels of binding sites were observed in the absence of potassium thiocyanate (KSCN), with binding predominantly found in telencephalic structures. The presence of KSCN induced a relatively uniform and large (four‐ to fivefold) increase in binding throughout the different brain structures. Pretreatment of the tissue sections with the SH– group reagent p ‐chloromercuriphenylsulfonic acid produced a 0.5‐ to 1.5‐fold increase in [ 3 H]AMPA binding. The enhanced binding displayed a regional variation with the largest increase in binding observed in the outer layer of the parietal cortex whereas the lowest increase occurred in the striatum. These results indicate that SH– group modification of tissue sections produces an increase in [ 3 H]AMPA binding similar to that observed in detergent‐treated membrane preparations. Moreover they reveal that [ 3 H]AMPA binding sites in different brain regions vary in their susceptibility to modification by SH– reagents, suggesting the existence in brain of a heterogeneous distribution of quisqualate/AMPA receptor subtypes.