Role of cerebellar granule cell-specific GABAA receptor subtype in the differential sensitivity of [3H]ethynylbicycloorthobenzoate binding to GABA mimetics.
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.
Huang
J
J
Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
Casida
J E
JE
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004726:Endosulfan / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D011963:Receptors, GABA-A; D005576:Colforsin; D004726:Endosulfan