Neurosteroid Modulation of GABAA Receptor Function by Independent Action at Multiple Specific Binding Sites
| Autor: | Lei Wang, Alex S. Evers, Gustav Akk, Douglas F. Covey |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Affinity labeling Neuroactive steroid Chemistry GABAA receptor Allopregnanolone Allosteric regulation General Medicine Psychiatry and Mental health chemistry.chemical_compound nervous system Neurology mental disorders Pharmacology (medical) Neurology (clinical) Binding site Receptor Neuroscience Ion channel |
| Zdroj: | Current Neuropharmacology. 20:886-890 |
| ISSN: | 1570-159X |
| DOI: | 10.2174/1570159x19666211202150041 |
| Popis: | Neurosteroids are endogenous modulators of GABAA receptors that mediate anxiety, pain, mood and arousal. The 3-hydroxyl epimers, allopregnanolone (3α-OH) and epiallopregnanolone (3β-OH) are both prevalent in the mammalian brain and produce opposite effects on GABAA receptor function, acting as positive and negative allosteric modulators, respectively. This Perspective provides a model to explain the actions of 3α-OH and 3β-OH neurosteroids. The model is based on evidence that the neurosteroid epimers bind to an overlapping subset of specific sites on GABAA receptors, with their net functional effect on channel gating being the sum of their independent effects at each site. |
| Databáze: | OpenAIRE |
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