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

Citation
St. Sinkkonen et al., Characterization of gamma-aminobutyrate type A receptors with atypical coupling between agonist and convulsant binding sites in discrete brain regions, MOL BRAIN R, 86(1-2), 2001, pp. 168-178
Citations number
39
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR BRAIN RESEARCH
ISSN journal
0169328X → ACNP
Volume
86
Issue
1-2
Year of publication
2001
Pages
168 - 178
Database
ISI
SICI code
0169-328X(20010131)86:1-2<168:COGTAR>2.0.ZU;2-J
Abstract
gamma -Aminobutyric acid type A (GABA(A)) receptor ionophore ligand t-[S-35 ]butylbicyclophosphorothionate ([S-35]TBPS) was used in an autoradiographic assay on brain cryostat sections to visualize and characterize atypical GA BA-insensitive [S-35]TBPS binding previously described in certain recombina nt GABA(A) receptors and the cerebellar granule cell layer. Picrotoxinin-se nsitive but 1-mM GABA-insensitive [S-35]TBPS binding was present in the rat cerebellar granule cell layer, many thalamic nuclei, subiculum and the int ernal rim of the cerebral cortex, amounting in these regions up to 6% of th e basal binding determined in the absence of exogenous GABA. Similar bindin g properties were detected also in human and chicken brain sections. Like t he GABA-sensitive [S-35]TBPS binding, GABA-insensitive binding was profound ly decreased by pentobarbital, pregnanolone, loreclezole and Mg2+. The bind ing was reversible and apparently dependent on Cl- ions. Localization of th e GABA-insensitive [S-35]TBPS binding was not identical to that of high-aff inity [H-3]muscimol binding and diazepam-insensitive [H-3]Ro 15-4513 bindin g, two previously established receptor subtype-dependent binding heterogene ities in the rat brain. The present study reveals a component of the GABA-i onophore enriched in the thalamus and cerebellar granule cells, possibly re presenting poorly desensitized or desensitizing receptors. (C) 2001 Elsevie r Science B.V. All rights reserved.