Is GPR146 really the receptor for proinsulin C-peptide?
C-peptide
Dynamic mass redistribution
Fluorescence microscopy
GPR146
β-Arrestin
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
20
02
2020
revised:
16
04
2020
accepted:
18
04
2020
pubmed:
2
5
2020
medline:
3
6
2021
entrez:
2
5
2020
Statut:
ppublish
Résumé
Proinsulin C-peptide has previously been proposed to interact with a G-protein coupled receptor (GPCR), specifically the orphan receptor GPR146. To investigate the potential of C-peptide in treating complications of diabetes, such as kidney damage, it is necessary to understand its mode of action. We used CHO-K1 cells expressing human GPR146 to study human and murine C-peptide in dynamic mass redistribution and GPCR β-arrestin assays, as well as with fluorescence confocal microscopy. Neither assay revealed any significant intracellular response to C-peptide at concentrations of up to 33 µM. We observed no internalisation of C-peptide by fluorescence microscopy. Our results do not support GPR146 as the receptor for C-peptide, but suggest that further investigations of the mode of action of C-peptide should be undertaken.
Identifiants
pubmed: 32354568
pii: S0960-894X(20)30308-5
doi: 10.1016/j.bmcl.2020.127208
pii:
doi:
Substances chimiques
C-Peptide
0
GPR146 protein, human
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127208Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.