Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00546861" target="_blank" >RIV/67985823:_____/21:00546861 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/21:00546861

Výsledek na webu

<a href="https://doi.org/10.1016/j.neuropharm.2021.108798" target="_blank" >https://doi.org/10.1016/j.neuropharm.2021.108798</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neuropharm.2021.108798" target="_blank" >10.1016/j.neuropharm.2021.108798</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptor

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/GA19-05318S" target="_blank" >GA19-05318S: Molekulární mechanismy alosterické modulace muskarinových receptorů pro acetylcholin neurosteroidy a cholesterolem</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neuropharmacology

ISSN

0028-3908

e-ISSN

1873-7064

Svazek periodika

199

Číslo periodika v rámci svazku

Nov 1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

13

Strana od-do

108798

Kód UT WoS článku

000703161100007

EID výsledku v databázi Scopus

2-s2.0-85115393333