Identification of N-acyl amino acids that are positive allosteric modulators of glycine receptors.
Allosteric Regulation
Amino Acids
/ chemistry
Animals
Binding Sites
Dose-Response Relationship, Drug
Female
Glycine
/ analogs & derivatives
Molecular Structure
Oleic Acids
/ chemistry
Oocytes
/ metabolism
Patch-Clamp Techniques
Protein Subunits
Receptors, Glycine
/ genetics
Small Molecule Libraries
/ chemistry
Structure-Activity Relationship
Xenopus laevis
Glycine receptor
Ligand-gated ion channel
Lipid
N-oleoyl glycine
Pain
Positive allosteric modulator
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
22
04
2020
revised:
16
06
2020
accepted:
18
06
2020
pubmed:
25
6
2020
medline:
12
1
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
Glycine receptors (GlyRs) mediate inhibitory neurotransmission within the spinal cord and play a crucial role in nociceptive signalling. This makes them primary targets for the development of novel chronic pain therapies. Endogenous lipids have previously been shown to modulate glycine receptors and produce analgesia in pain models, however little is known about what chemical features mediate these effects. In this study, we characterised lipid modulation of GlyRs by screening a library of N-acyl amino acids across all receptor subtypes and determined chemical features crucial for their activity. Acyl-glycine's with a C18 carbon tail were found to produce the greatest potentiation, and require a cis double bond within the central region of the carbon tail (ω6 - ω9) to be active. At 1 µM, C18 ω6,9 glycine potentiated glycine induced currents in α
Identifiants
pubmed: 32579961
pii: S0006-2952(20)30353-1
doi: 10.1016/j.bcp.2020.114117
pii:
doi:
Substances chimiques
Amino Acids
0
N-oleoylglycine
0
Oleic Acids
0
Protein Subunits
0
Receptors, Glycine
0
Small Molecule Libraries
0
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114117Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.