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Vol. 56, Issue 1, 110-115, July 1999

Preferential Coassembly of alpha 4 and delta  Subunits of the gamma -Aminobutyric AcidA Receptor in Rat Thalamus

Cyrille Sur, Sophie J. Farrar, Julie Kerby, Paul J. Whiting, John R. Atack, and Ruth M. McKernan

Department of Biochemistry and Molecular Biology, Neuroscience Research Centre, Merck Research Laboratories, Harlow, Essex, United Kingdom

Pharmacological study of rat thalamic gamma -aminobutyric acidA (GABAA) receptors revealed the presence of two distinct populations, namely, diazepam-sensitive and diazepam-insensitive [3H]Ro15-4513 binding sites accounting for 94 ± 2% (1339 ± 253 fmol/mg protein) and 6 ± 2% (90 ± 44 fmol/mg protein) of total sites, respectively. Thalamic diazepam-insensitive sites exhibited a pharmacology that was distinct from diazepam-sensitive sites but comparable to that of the alpha 4beta 3gamma 2 subtype of the GABAA receptor stably expressed in L(tk-) cells. Immunoprecipitation experiments with a specific anti-alpha 4-antiserum immunoprecipitated 20 and 7% of total thalamic [3H]muscimol and [3H]Ro15-4513 sites, respectively. Combinatorial immunoprecipitation using antisera against the alpha 4, gamma 2, and delta  subunit revealed that alpha 4delta - and alpha 4gamma 2-containing receptors account for 13 ± 2 and 8 ± 3% of [3H]muscimol sites from thalamus, respectively. It also indicated that all delta  subunits coexist with an alpha 4 subunit in this brain region. In conclusion, our results show that in rat thalamus both alpha 4beta gamma 2 and alpha 4beta delta subtypes are expressed but alpha 4beta delta is the major alpha 4-containing GABAA receptor population.


Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics



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