Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptors.
Allosteric modulation
Muscarinic receptor
Neurosteroid
Steroid hormone
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
15
01
2021
revised:
07
09
2021
accepted:
16
09
2021
pubmed:
24
9
2021
medline:
31
3
2022
entrez:
23
9
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34555368
pii: S0028-3908(21)00353-1
doi: 10.1016/j.neuropharm.2021.108798
pii:
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Gonadal Steroid Hormones
0
Neurosteroids
0
Receptors, Muscarinic
0
Progesterone
4G7DS2Q64Y
Acetylcholine
N9YNS0M02X
Corticosterone
W980KJ009P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108798Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.