Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites

  title={Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites},
  author={Alastair M. Hosie and Megan E. Wilkins and Helena da Silva and Trevor G. Smart},
Inhibitory neurotransmission mediated by GABAA receptors can be modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone. Neurosteroids are synthesized de novo in the brain during stress, pregnancyand after ethanol consumption, and disrupted steroid regulation of GABAergic transmission is strongly implicated in several debilitating conditions such as panic disorder, major depression, schizophrenia, alcohol dependence and catamenial epilepsy. Determining how… 
Inhibitory neurosteroids and the GABAA receptor.
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Neuroactive steroids do not require direct aqueous access to the receptor, and membrane accumulation is required for receptor modulation, according to current views of receptor modulation.
The Contraceptive Agent Provera Enhances GABAA Receptor-Mediated Inhibitory Neurotransmission in the Rat Hippocampus: Evidence for Endogenous Neurosteroids?
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Neurosteroids: endogenous regulators of the GABAA receptor
GABAA (γ-aminobutyric acid type A) receptors mediate most of the 'fast' synaptic inhibition in the mammalian brain and are targeted by many clinically important drugs. Certain naturally occurring
Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms.
An overview of recent data pertaining to mechanisms that could be responsible for altered properties and expression of GABA(A) receptors following chronic ethanol administration is provided.
Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABAA receptors
It is reported that, at concentrations known to occur in vivo, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons that is mediated by extrasynaptic δ subunit-containing GABAARs.
Neurosteroid Biosynthesis in the Human Brain and Its Clinical Implications
Improved knowledge of the biochemical pathways of neurosteroidogenesis and their actions on the brain may enable new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.