Regional Distribution of α‐[3H]Amino‐3‐Hydroxy‐5‐Methylisoxazole‐4‐Propionic Acid Binding Sites in Rat Brain: Effect of Chemical Modification of SH– Groups in Tissue Sections

Michel Baudry, Daniel Monaghan, Carl Cotman, C. Anthony Altar

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Abstract

Abstract: Previous studies have shown that chemical modifications of sulfhydryl (SH–) groups with mercurial compounds in rat brain membrane preparations increase the binding of α‐[3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid ([3H]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 [3H]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 [3H]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 [3H]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 [3H]AMPA binding similar to that observed in detergent‐treated membrane preparations. Moreover they reveal that [3H]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.

Original languageEnglish (US)
Pages (from-to)1682-1688
Number of pages7
JournalJournal of Neurochemistry
Volume54
Issue number5
DOIs
StatePublished - May 1990

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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Chemical modification
Rats
Brain
Binding Sites
AMPA Receptors
Tissue
Acids
Sulfhydryl Reagents
Quisqualic Acid
Telencephalon
Parietal Lobe
Membranes
Glutamate Receptors
Ligands
potassium thiocyanate
Chemical analysis

Keywords

  • Autoradiography
  • Brain section
  • Excitotoxicity
  • Glutamate receptors
  • Huntington's disease
  • Striatum
  • Sulfhydryl groups

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Regional Distribution of α‐[3H]Amino‐3‐Hydroxy‐5‐Methylisoxazole‐4‐Propionic Acid Binding Sites in Rat Brain: Effect of Chemical Modification of SH– Groups in Tissue Sections",
abstract = "Abstract: Previous studies have shown that chemical modifications of sulfhydryl (SH–) groups with mercurial compounds in rat brain membrane preparations increase the binding of α‐[3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid ([3H]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 [3H]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 [3H]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 [3H]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 [3H]AMPA binding similar to that observed in detergent‐treated membrane preparations. Moreover they reveal that [3H]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.",
keywords = "Autoradiography, Brain section, Excitotoxicity, Glutamate receptors, Huntington's disease, Striatum, Sulfhydryl groups",
author = "Michel Baudry and Daniel Monaghan and Carl Cotman and Altar, {C. Anthony}",
year = "1990",
month = "5",
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language = "English (US)",
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T1 - Regional Distribution of α‐[3H]Amino‐3‐Hydroxy‐5‐Methylisoxazole‐4‐Propionic Acid Binding Sites in Rat Brain

T2 - Effect of Chemical Modification of SH– Groups in Tissue Sections

AU - Baudry, Michel

AU - Monaghan, Daniel

AU - Cotman, Carl

AU - Altar, C. Anthony

PY - 1990/5

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N2 - Abstract: Previous studies have shown that chemical modifications of sulfhydryl (SH–) groups with mercurial compounds in rat brain membrane preparations increase the binding of α‐[3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid ([3H]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 [3H]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 [3H]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 [3H]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 [3H]AMPA binding similar to that observed in detergent‐treated membrane preparations. Moreover they reveal that [3H]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.

AB - Abstract: Previous studies have shown that chemical modifications of sulfhydryl (SH–) groups with mercurial compounds in rat brain membrane preparations increase the binding of α‐[3H]‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid ([3H]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 [3H]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 [3H]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 [3H]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 [3H]AMPA binding similar to that observed in detergent‐treated membrane preparations. Moreover they reveal that [3H]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.

KW - Autoradiography

KW - Brain section

KW - Excitotoxicity

KW - Glutamate receptors

KW - Huntington's disease

KW - Striatum

KW - Sulfhydryl groups

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