Identification of aurintricarboxylic acid as a potent allosteric antagonist of P2X1 and P2X3 receptors.
Allosteric Regulation
Allosteric Site
Animals
Aurintricarboxylic Acid
/ pharmacology
Ganglia, Spinal
/ cytology
High-Throughput Screening Assays
Humans
Mice
Molecular Docking Simulation
Neurons
/ drug effects
Oocytes
Patch-Clamp Techniques
Purinergic P2X Receptor Antagonists
/ pharmacology
Rats
Receptors, Purinergic P2X1
/ drug effects
Receptors, Purinergic P2X3
/ drug effects
Xenopus laevis
Allosteric P2X3 antagonist
Drug-like P2X3 antagonist
High-throughput drug screening
Ligand docking
P2X3 receptor
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
03
07
2019
revised:
14
08
2019
accepted:
23
08
2019
pubmed:
29
8
2019
medline:
21
7
2020
entrez:
29
8
2019
Statut:
ppublish
Résumé
The homotrimeric P2X3 receptor, one of the seven members of the ATP-gated P2X receptor family, plays a crucial role in sensory neurotransmission. P2X3 receptor antagonists have been identified as promising drugs to treat chronic cough and are suggested to offer pain relief in chronic pain such as neuropathic pain. Here, we analysed whether compounds affect P2X3 receptor activity by high-throughput screening of the Spectrum Collection of 2000 approved drugs, natural products and bioactive substances. We identified aurintricarboxylic acid (ATA) as a nanomolar-potency antagonist of P2X3 receptor-mediated responses. Two-electrode voltage clamp electrophysiology-based concentration-response analysis and selectivity profiling revealed that ATA strongly inhibits the rP2X1 and rP2X3 receptors (with IC
Identifiants
pubmed: 31461640
pii: S0028-3908(19)30308-9
doi: 10.1016/j.neuropharm.2019.107749
pii:
doi:
Substances chimiques
Purinergic P2X Receptor Antagonists
0
Receptors, Purinergic P2X1
0
Receptors, Purinergic P2X3
0
Aurintricarboxylic Acid
4431-00-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107749Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.