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Molecular Pharmacology

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Abstract

Impact of beta and gamma variants on ligand-binding properties of gamma-aminobutyric acid type A receptors.

H Lüddens, P H Seeburg and E R Korpi
Molecular Pharmacology May 1994, 45 (5) 810-814;
H Lüddens
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P H Seeburg
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E R Korpi
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Abstract

We expressed in cultured cells recombinant gamma-aminobutyric acid type A (GABAA) receptors of the subunit compositions alpha 1 beta j gamma k and alpha 5 beta j gamma k (j = 1, 2, or 3 and k = 2 or 3). A comparison of ligand-binding properties revealed a functional role for individual beta variants, which depended on the alpha subunit in the GABAA receptor. Recombinant alpha 5 beta x gamma 2/3 receptors recognized the cage convulsant t-butylbicyclophosphoro[35S]thionate, as well as the benzodiazepine (BZ) receptor inverse agonist [3H]Ro 15-4513, only with the beta 3 variant. In contrast, the exchange of beta variants in alpha 1 beta x gamma 2 receptors imparted differential modulation of t-butyl-bicyclophosphoro[35S]thionate binding by BZ receptor ligands. The BZ site of gamma 3-containing receptors was partially independent of the accompanying alpha and beta variants. alpha 1/5 beta 3 gamma 3 receptors were zolpidem insensitive but distinguished from alpha 5 beta 3 gamma 2 receptors by high affinity for the partial BZ receptor agonist CI 218,872. The distinct affinities of recombinant receptors for CI 218,872 suggested that the alpha 5 beta 3 gamma 2 receptor is the dominant zolpidem-insensitive GABAA receptor in the brain. Hence, alpha 5 beta 3 gamma 3 recpetors are not a major fraction of the native zolpidem-insensitive receptors, even though their genes are colocalized on mouse chromosome 7 and on human chromosome 15.

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Molecular Pharmacology
Vol. 45, Issue 5
1 May 1994
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Abstract

Impact of beta and gamma variants on ligand-binding properties of gamma-aminobutyric acid type A receptors.

H Lüddens, P H Seeburg and E R Korpi
Molecular Pharmacology May 1, 1994, 45 (5) 810-814;

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Abstract

Impact of beta and gamma variants on ligand-binding properties of gamma-aminobutyric acid type A receptors.

H Lüddens, P H Seeburg and E R Korpi
Molecular Pharmacology May 1, 1994, 45 (5) 810-814;
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