Role of cerebellar granule cell-specific GABAA receptor subtype in the differential sensitivity of [3H]ethynylbicycloorthobenzoate binding to GABA mimetics.

Abstract:

:Binding of [3H]ethynylbicycloorthobenzoate ([3H]EBOB) to the gamma-aminobutyric acid type A (GABAA) receptor of cultured cerebellar granule neurons is inhibited by GABA, muscimol and 3-aminopropanesulfonic acid with IC50 values of 69-250 nM. Sensitivity to these GABA mimetics is lower by 3-4-fold for cerebellum and 10-20-fold for cerebral cortex, midbrain, and pons and medulla, a differential sensitivity by brain region and cell type consistent with earlier findings using tert-[35S]butylbicyclophosphorothionate and GABA. In contrast, the inhibitory potencies of two chloride channel blockers, alpha-endosulfan and picrotoxinin, do not differ in these assays. The hypothesis that this pharmacological profile is conferred by the alpha 6 subunit specific to cerebellar granule cells is supported by the finding that forskolin (which downregulates the alpha 6 subunit) but not the inactive dideoxyforskolin markedly decreases the sensitivity of [3H]EBOB binding to GABA without affecting inhibition by alpha-endosulfan.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Huang J,Casida JE

doi

10.1016/s0304-3940(97)00206-1

subject

Has Abstract

pub_date

1997-04-04 00:00:00

pages

85-8

issue

2

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(97)00206-1

journal_volume

225

pub_type

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