title: Bidirectional regulation of GABAA receptor alpha1 and alpha6 subunit expression by a cyclic AMP-mediated signalling mechanism in cerebellar granule cells in primary culture.
abstract: Forskolin treatment of cerebellar granule cells in culture resulted in bidirectional regulation of the expression of GABAA receptor alpha1 and alpha6 subunits. Thus, forskolin applied at 2 days in vitro (DIV) increased expression of the alpha1 subunit but decreased the expression of the alpha6 subunit. Values with respect to control cultures, both assayed at 9 DIV by immunoblotting, were 310 +/- 48% for alpha1 and 25 +/- 16% for the alpha6 subunit. Similar effects were evoked following chronic treatment with both dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine. Dideoxyforskolin had no effect on the level of expression of either the alpha1 or the alpha6 GABAA receptor subunits. The changes in subunit expression were accompanied by a 1.7-fold increase in number of total specific [3H]Ro 15-4513 binding sites expressed by intact cerebellar granule cells. This increase in total binding sites was accommodated by a 2.7-fold increase in number of diazepam-sensitive Ro 15-4513 binding sites in accordance with the observed increase in alpha1 subunit expression. The number of diazepam-insensitive subtype of binding sites were not significantly changed. These results suggest that GABAA receptor subtype expression can be differentially regulated by intracellular cyclic AMP concentration.
authors.affiliation: Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University of London, England.
authors.forename: C L
authors.initials: CL
authors.lastname: Thompson
authors.forename: S
authors.initials: S
authors.lastname: Pollard
authors.forename: F A
authors.initials: FA
authors.lastname: Stephenson
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured / Q000737:chemistry / Q000502:physiology; D002531:Cerebellum / Q000166:cytology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014316:Tritium / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D001386:Azides; D010726:Phosphodiesterase Inhibitors; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005576:Colforsin; D003994:Bucladesine; C042957:Ro 15-4513; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine