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Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor
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SYSNO ASEP 0546861 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor Author(s) Dolejší, Eva (FGU-C) RID, ORCID
Szánti-Pintér, Eszter (UOCHB-X) ORCID
Chetverikov, Nikolai (FGU-C) RID, ORCID, SAI
Nelic, Dominik (FGU-C) ORCID, RID
Randáková, Alena (FGU-C) RID, ORCID
Doležal, Vladimír (FGU-C) RID, ORCID
Kudová, Eva (UOCHB-X) RID, ORCID
Jakubík, Jan (FGU-C) RID, ORCIDArticle number 108798 Source Title Neuropharmacology. - : Elsevier - ISSN 0028-3908
Roč. 199, Nov 1 (2021)Number of pages 13 s. Language eng - English Country NL - Netherlands Keywords neurosteroid ; steroid hormone ; allosteric modulation ; muscarinic receptor Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GA19-05318S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963 UT WOS 000703161100007 EID SCOPUS 85115393333 DOI 10.1016/j.neuropharm.2021.108798 Annotation The membrane cholesterol was found to bind and modulate the function of several G-protein coupled receptors including muscarinic acetylcholine receptors. We investigated the binding of 20 steroidal compounds including neurosteroids and steroid hormones to muscarinic receptors. Corticosterone, progesterone and some neurosteroids bound to muscarinic receptors with the affinity of 100 nM or greater. We established a structure-activity relationship for steroid-based allosteric modulators of muscarinic receptors. Further, we show that corticosterone and progesterone allosterically modulate the functional response of muscarinic receptors to acetylcholine at physiologically relevant concentrations. It can play a role in stress control or in pregnancy, conditions where levels of these hormones dramatically oscillate. Allosteric modulation of muscarinic receptors via the cholesterol binding site represents a new pharmacological approach at diseases associated with altered cholinergic signalling. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1016/j.neuropharm.2021.108798
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