DOI:10.1016/0896-6273(90)90202-Q - Corpus ID: 12626366
Neurosteroids act on recombinant human GABAA receptors
@article{Puia1990NeurosteroidsAO, title={Neurosteroids act on recombinant human GABAA receptors}, author={Giulia Puia and Maria Rita Santi and Stefano Vicini and Dolan B. Pritchett and Robert H. Purdy and Steven M. Paul and P. H. Seeburg and Erminio Costa}, journal={Neuron}, year={1990}, volume={4}, pages={759-765}, url={https://api.semanticscholar.org/CorpusID:12626366} }
539 Citations
539 Citations
Neurosteroid: Molecular Mechanisms of Action on the GABAA Receptor
- Mingde WangMozibur Rahman Torbjörn Bückström
- Medicine, Biology
- 2008
The molecular mechanisms underpinning the non-genomic effect of agonist and antagonist neurosteroids will be discussed with particular emphasis being given to the role of GABA A receptor isoforms.
The Selective Interaction of Neurosteroids with the GABA A Receptor
It was not until Harrison and Simmonds demonstrated that a synthetic steroidal anesthetic, alphaxalone (3α-hydroxy-5α-pregnane-11,20-dione), selectively enhanced the interaction of GABA with the GABAA receptor, that a logical mechanism to explain the behavioral effects of these compounds emerged.
Steroid Modulation of GABAA Receptors
- J. LambertJ. A. PetersS. HarneyD. Belelli
- Medicine, Chemistry
- 2001
In electrophysiological, tracer-flux and radioligand binding studies, such steroids were found to be more potent than alphaxalone in potentiating the action of agonists at the GABAA receptor and allosteric interactions with established binding sites for other modulators were revealed.
3β-Hydroxypregnane Steroids Are Pregnenolone Sulfate-Like GABAA Receptor Antagonists
- Mingde WangYejun He S. Mennerick
- Chemistry, Medicine
- 2002
3β-hydroxypregnane steroids are not direct antagonists of potentiating steroids but rather are noncompetitive, likely state-dependent, blockers of GABAAreceptors Nevertheless, these steroids may be useful functional blockers of potentiation steroids when used at concentrations that do not affect baseline neurotransmission.
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25 References
Modulation of the GABAA receptor by progesterone metabolites
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- Biology, ChemistryProceedings of the Royal Society of London…
- 1987
The results suggest that certain naturally occurring steroids potentiate the actions of GABA and, additionally, directly activate the GABAA receptor.
Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.
- MajewskaN. HarrisonR. D. SchwartzJ. BarkerS. Paul
- Medicine, Chemistry
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Two metabolites of the steroid hormones progesterone and deoxycorticosterone are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons, which may explain the ability of certain steroid hormones to rapidly alter neuronal excitability.
Synthesis, metabolism, and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes.
Molecular modeling of the active steroids based on quantitative structure-activity relationships provides evidence to support the stereospecificity of the binding interactions and suggests that there may be more than one type of steroid binding site associated with the GABAA-receptor-mediated chloride ionophore.
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
- D. B. PritchettH. Sontheimer P. Seeburg
- Medicine
- 1989
The isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS.
Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids
- J. A. PetersE. KirknessH. CallachanJ. LambertA. Turner
- Chemistry, Medicine
- 1988
The results obtained with combinations of steroids and barbiturates in the ligand binding assay appear inconsistent with the two classes of compound interacting with a common site to modulate the GABAA receptor activity.
Structural and functional basis for GABAA receptor heterogeneity
- E. LevitanPeter R. Schofield P. Seeburg
- Biology
- 1988
Two additional cDNAs encoding two additional GABAA receptor α-subunits are isolated, confirming the heterogeneous nature of the receptor/chloride channel complex and demonstrating the molecular basis for it.
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