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Vol. 56, Issue 1, 110-115, July 1999
4 and
Subunits of the
-Aminobutyric AcidA Receptor in Rat Thalamus
Department of Biochemistry and Molecular Biology, Neuroscience
Research Centre, Merck Research Laboratories, Harlow, Essex, United
Kingdom
Pharmacological study of rat thalamic
-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
4
3
2 subtype of the GABAA
receptor stably expressed in L(tk-) cells.
Immunoprecipitation experiments with a specific anti-
4-antiserum immunoprecipitated 20 and 7% of total thalamic
[3H]muscimol and [3H]Ro15-4513 sites,
respectively. Combinatorial immunoprecipitation using antisera against
the
4,
2, and
subunit revealed that
4
- and
4
2-containing receptors account for 13 ± 2 and 8 ± 3% of [3H]muscimol sites from thalamus, respectively. It
also indicated that all
subunits coexist with an
4 subunit in
this brain region. In conclusion, our results show that in rat thalamus
both
4
2 and
4
subtypes are expressed but
4
is the major
4-containing GABAA receptor population.
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