A photoreactive analog of allopregnanolone enables identification of steroid-binding sites in a nicotinic acetylcholine receptor.

ABSTRACT: Many neuroactive steroids potently and allosterically modulate pentameric ligand-gated ion channels, including GABA_A receptors (GABA_AR) and nicotinic acetylcholine receptors (nAChRs). Allopregnanolone and its synthetic analog alphaxalone are GABA_AR-positive allosteric modulators (PAMs), whereas alphaxalone and most neuroactive steroids are nAChR inhibitors. In this report, we used 11β-(p-azidotetrafluorobenzoyloxy)allopregnanolone (F₄N₃Bzoxy-AP), a general anesthetic and photoreactive allopregnanolone analog that is a potent GABA_AR PAM, to characterize steroid-binding sites in the Torpedo α₂βγδ nAChR in its native membrane environment. We found that F₄N₃Bzoxy-AP (IC₅₀

SUBMITTER: Yu Z 

PROVIDER: S-EPMC6514614 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature