Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor

Dolejší, Eva; Szánti-Pintér, Eszter; Chetverikov, Nikolai; Nelic, Dominik; Randáková, Alena; Doležal, Vladimír; Kudová, Eva; Jakubík, Jan

doi:https://dx.doi.org/10.1016/j.neuropharm.2021.108798

Počet záznamů: 1

Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor

1.

SYSNO ASEP	0546861
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor
Tvůrce(i)	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, ORCID}
Číslo článku	108798
Zdroj.dok.	Neuropharmacology. - : Elsevier - ISSN 0028-3908 Roč. 199, Nov 1 (2021)
Poč.str.	13 s.
Jazyk dok.	eng - angličtina
Země vyd.	NL - Nizozemsko
Klíč. slova	neurosteroid ; steroid hormone ; allosteric modulation ; muscarinic receptor
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	000703161100007
EID SCOPUS	85115393333
DOI	10.1016/j.neuropharm.2021.108798
Anotace	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.
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.neuropharm.2021.108798

Počet záznamů: 1