Characterization of gamma-aminobutyrate type A receptors with atypical coupling between agonist and convulsant binding sites in discrete brain regions |
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Authors: | Sinkkonen S T Uusi-Oukari M Tupala E Särkioja T Tiihonen J Panula P Lüddens H Korpi E R |
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Institution: | Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland. |
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Abstract: | Gamma-ainobutyric acid type A (GABA(A)) receptor ionophore ligand t-35S]butylbicyclophosphorothionate (35S]TBPS) was used in an autoradiographic assay on brain cryostat sections to visualize and characterize atypical GABA-insensitive 35S]TBPS binding previously described in certain recombinant GABA(A) receptors and the cerebellar granule cell layer. Picrotoxinin-sensitive but 1-mM GABA-insensitive 35S]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 35S]TBPS binding, GABA-insensitive binding was profoundly decreased by pentobarbital, pregnanolone, loreclezole and Mg2+. The binding was reversible and apparently dependent on Cl- ions. Localization of the GABA-insensitive 35S]TBPS binding was not identical to that of high-affinity 3H]muscimol binding and diazepam-insensitive 3H]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. |
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