A New Model of Sensorial Neuron-Like Cells for HTS of Novel Analgesics for Neuropathic Pain.
Adenosine Triphosphate
/ pharmacology
Analgesics
/ pharmacology
Animals
Cell Differentiation
/ drug effects
Cell Line
Ganglia, Spinal
/ drug effects
High-Throughput Screening Assays
/ methods
Humans
Inhibitory Concentration 50
Models, Biological
Neuralgia
/ drug therapy
Neurons
/ drug effects
Potassium Chloride
/ pharmacology
F11 cells
HTS
differentiation
immunofluorescence
neuronal excitability
neuropathic pain
Journal
SLAS discovery : advancing life sciences R & D
ISSN: 2472-5560
Titre abrégé: SLAS Discov
Pays: United States
ID NLM: 101697563
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
2
11
2018
medline:
28
3
2020
entrez:
2
11
2018
Statut:
ppublish
Résumé
In this study we developed a new translational phenotypic in vitro model for high-throughput screening (HTS) of novel analgesics for treating neuropathic pain, in order to address the poor translation of traditional recombinant models. The immortalized dorsal root ganglia (DRG) neuron-like F11 cell line was selected based on its phenotype after differentiation. The acquisition of neuronal characteristics was evaluated by measuring the expression of TrkA as a DRG neuron marker ( p < 0.01) as well as by measuring the global neurite length ( p < 0.001). The response of F11 cells to ATP and KCl was obtained by measuring intracellular calcium concentration, dynamic mass redistribution, and membrane potential. A KCl-induced increase of intracellular calcium levels was chosen as the readout because of the better signal quality, higher reproducibility, and greater compatibility with HTS assay requirements compared with other methods. The response to KCl differed significantly between differentiated and undifferentiated cells ( p < 0.05), with an EC
Identifiants
pubmed: 30383474
doi: 10.1177/2472555218810323
pii: S2472-5552(22)12565-7
doi:
Substances chimiques
Analgesics
0
Potassium Chloride
660YQ98I10
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM