6533b830fe1ef96bd129705b

RESEARCH PRODUCT

Characterization of γ-aminobutyrate type A receptors with atypical coupling between agonist and convulsant binding sites in discrete brain regions

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Abstract γ-Aminobutyric acid type A (GABA A ) receptor ionophore ligand t -[ 35 S]butylbicyclophosphorothionate ([ 35 S]TBPS) was used in an autoradiographic assay on brain cryostat sections to visualize and characterize atypical GABA-insensitive [ 35 S]TBPS binding previously described in certain recombinant GABA A receptors and the cerebellar granule cell layer. Picrotoxinin-sensitive but 1-mM GABA-insensitive [ 35 S]TBPS binding was present in the rat cerebellar granule cell layer, many thalamic nuclei, subiculum and the internal rim of the cerebral cortex, amounting in these regions up to 6% of the basal binding determined in the absence of exogenous GABA. Similar binding properties were detected also in human and chicken brain sections. Like the GABA-sensitive [ 35 S]TBPS binding, GABA-insensitive binding was profoundly decreased by pentobarbital, pregnanolone, loreclezole and Mg 2+ . The binding was reversible and apparently dependent on Cl − ions. Localization of the GABA-insensitive [ 35 S]TBPS binding was not identical to that of high-affinity [ 3 H]muscimol binding and diazepam-insensitive [ 3 H]Ro 15-4513 binding, two previously established receptor subtype-dependent binding heterogeneities in the rat brain. The present study reveals a component of the GABA-ionophore enriched in the thalamus and cerebellar granule cells, possibly representing poorly desensitized or desensitizing receptors.