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Sites of positive allosteric modulation by neurosteroids on ionotropic γ‐aminobutyric acid receptor subunits
Author(s) -
Ueno Susumu,
Tsutsui Masato,
Toyohira Yumiko,
Minami Kouichiro,
Yanagihara Nobuyuki
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.04.030
Subject(s) - ionotropic effect , allosteric regulation , neuroactive steroid , aminobutyric acid , chemistry , allosteric modulator , gabaa receptor , receptor , biochemistry , pharmacology , biology , glutamate receptor
Neurosteroids are known as allosteric modulators of ionotropic γ‐aminobutyric acid (GABA) receptors. Here, we investigated sites of positive allosteric modulation by allotetrahydrodeoxycorticosterone (5α‐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 α1 subunit is crucial for the action of 5α‐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.