Neuroactive steroids, WIN-compounds and cholesterol share a common binding site on muscarinic acetylcholine receptors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00546864" target="_blank" >RIV/67985823:_____/21:00546864 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/21:00546864
Result on the web
<a href="https://doi.org/10.1016/j.bcp.2021.114699" target="_blank" >https://doi.org/10.1016/j.bcp.2021.114699</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2021.114699" target="_blank" >10.1016/j.bcp.2021.114699</a>

Result language
angličtina
Original language name
Neuroactive steroids, WIN-compounds and cholesterol share a common binding site on muscarinic acetylcholine receptors
Original language description
Endogenous neurosteroids and their synthetic analogues-neuroactive steroids-have been found to bind to muscarinic acetylcholine receptors and allosterically modulate acetylcholine binding and function. Using radioligand binding experiments we investigated their binding mode. We show that neuroactive steroids bind to two binding sites on muscarinic receptors. Their affinity for the high-affinity binding site is about 100 nM. Their affinity for the low-affinity binding site is about 10 mu M. The high-affinity binding occurs at the same site as binding of steroid-based WIN-compounds that is different from the common allosteric binding site for alcumnium or gallamine that is located between the second and third extracellular loop of the receptor. This binding site is also different from the allosteric binding site for the structurally related aminosteroid-based myorelaxants pancuronium and rapacuronium. Membrane cholesterol competes with neurosteroids/neuroactive steroids binding to both high- and low-affinity binding site, indicating that both sites are oriented towards the cell membrane.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30105 - Physiology (including cytology)

Project
<a href="/en/project/GA19-05318S" target="_blank" >GA19-05318S: Molecular mechanisms of allosteric modulation of muscarinic acetylcholine receptors by neurosteroids and cholesterol</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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