Regional distribution of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites in rat brain: effect of chemical modification of SH- groups in tissue sections.

Article date: 1990/5/1

PubMed ID: 2157815

Journal name: Journal of neurochemistry (ISSN: 0022-3042)


Previous studies have shown that chemical modifications of sulfhydryl (SH-) groups with mercurial compounds in rat brain membrane preparations increase the binding of alpha-[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.

Author List: Baudry M, Monaghan D, Cotman C, Altar C A

Publication Types: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.

Substances mentioned in the article: Oxazoles; Sulfhydryl Compounds; Thiocyanates; Ibotenic Acid; 4-Chloromercuribenzenesulfonate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; potassium thiocyanate;

Mesh terms: 4-Chloromercuribenzenesulfonate/pharmacology; Animals; Autoradiography; Binding Sites/drug effects; Brain/metabolism; Ibotenic Acid/analogs & derivatives; Male; Oxazoles/metabolism; Rats; Rats, Inbred Strains; Subtraction Technique; Sulfhydryl Compounds/metabolism; Thiocyanates/pharmacology; Tissue Distribution; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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