Abstract
Neurosteroids are known as allosteric modulators of ionotropic gamma-aminobutyric acid (GABA) receptors. Here, we investigated sites of positive allosteric modulation by allotetrahydrodeoxycorticosterone (5alpha-THDOC) at GABA receptors using the technique of chimeragenesis and the Xenopus oocyte expression system. Our findings have demonstrated that the region from transmembrane segment (TM) 4 to the C-terminus of the GABA(A) receptor alpha1 subunit is crucial for the action of 5alpha-THDOC, but insufficient for the action of another neurosteroid allopregnanolone, suggesting that a specific region critical for neurosteroid action at GABA receptors exists in the domain between TM4 and the C-terminus of GABA receptor subunits.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Allosteric Site
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Amino Acid Sequence
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Animals
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Conserved Sequence
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Desoxycorticosterone / analogs & derivatives*
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Desoxycorticosterone / pharmacology*
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Dose-Response Relationship, Drug
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Electrophysiology
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Female
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GABA-A Receptor Agonists*
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Humans
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Molecular Sequence Data
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Oocytes / drug effects
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Oocytes / metabolism
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Pregnanolone / pharmacology*
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Protein Subunits
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Receptors, GABA-A / chemistry
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Receptors, GABA-A / genetics
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Recombinant Proteins / agonists
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Xenopus Proteins / agonists
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Xenopus Proteins / chemistry
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Xenopus Proteins / genetics
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Xenopus laevis
Substances
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GABA-A Receptor Agonists
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Protein Subunits
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Receptors, GABA-A
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Recombinant Proteins
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Xenopus Proteins
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Desoxycorticosterone
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tetrahydrodeoxycorticosterone
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Pregnanolone