Mechanisms of neurosteroid interactions with GABA(A) receptors.
Neuroactive steroids have some of their most potent actions by augmenting the function of GABA(A) receptors. Endogenous steroid actions on GABA(A) receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA(A) receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.
Akk
Gustav
G
Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
Covey
Douglas F
DF
Evers
Alex S
AS
Steinbach
Joe Henry
JH
Zorumski
Charles F
CF
Mennerick
Steven
S
D000818:Animals; D001665:Binding Sites; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D013256:Steroids