Počet záznamů: 1
Neuroactive steroids, WIN-compounds and cholesterol share a common binding site on muscarinic acetylcholine receptors
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SYSNO ASEP 0546864 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Neuroactive steroids, WIN-compounds and cholesterol share a common binding site on muscarinic acetylcholine receptors Tvůrce(i) Dolejší, Eva (FGU-C) RID, ORCID
Chetverikov, Nikolai (FGU-C) RID, ORCID, SAI
Szánti-Pintér, Eszter (UOCHB-X) ORCID
Nelic, Dominik (FGU-C) ORCID, RID
Randáková, Alena (FGU-C) RID, ORCID
Doležal, Vladimír (FGU-C) RID, ORCID
El-Fakahany, E. E. (US)
Kudová, Eva (UOCHB-X) RID, ORCID
Jakubík, Jan (FGU-C) RID, ORCIDČíslo článku 114699 Zdroj.dok. Biochemical Pharmacology. - : Elsevier - ISSN 0006-2952
Roč. 192, Oct (2021)Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova neuroactive steroids ; cholesterol ; muscarinic receptors ; allosteric modulation Vědní obor RIV ED - Fyziologie Obor OECD Physiology (including cytology) CEP GA19-05318S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963 UT WOS 000701938400005 EID SCOPUS 85111566505 DOI https://doi.org/10.1016/j.bcp.2021.114699 Anotace 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. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2022 Elektronická adresa https://doi.org/10.1016/j.bcp.2021.114699
Počet záznamů: 1