A New Model of Sensorial Neuron-Like Cells for HTS of Novel Analgesics for 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
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

Pagination

158-168

Auteurs

Antón L Martínez (AL)

1 BioFarma Research Group, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.

José Brea (J)

1 BioFarma Research Group, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.

Xavier Monroy (X)

2 Esteve Pharmaceuticals, Parc Cientific de Barcelona, Barcelona, Spain.

Manuel Merlos (M)

2 Esteve Pharmaceuticals, Parc Cientific de Barcelona, Barcelona, Spain.

Javier Burgueño (J)

2 Esteve Pharmaceuticals, Parc Cientific de Barcelona, Barcelona, Spain.

María Isabel Loza (MI)

1 BioFarma Research Group, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.

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Classifications MeSH