An intact model for quantifying functional selectivity.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 02 2019
22 02 2019
Historique:
received:
18
05
2018
accepted:
04
01
2019
entrez:
24
2
2019
pubmed:
24
2
2019
medline:
20
9
2020
Statut:
epublish
Résumé
A ligand that acts on a target receptor to activate particular multiple signalling pathways with activity that is distinct from other ligands is termed ligand bias. Quantification of ligand bias is based on applying the operational model to each pathway separately and subsequent calculation of the ligand bias metric (ΔΔlogR). This approach implies independence among different pathways and causes propagation of error in the calculation. Here, we propose a semi-mechanism-based model which allows for receptor selectivity across all the pathways simultaneously (termed the 'intact operational model'). The power of the intact model for detecting ligand bias was evaluated via stochastic simulation estimation studies. It was also applied to two examples: (1) opposing effects of Gi/Gs signalling of α2-adrenergic receptors and (2) simultaneous measurement of arachidonic acid release and inositol phosphate accumulation following 5-HT
Identifiants
pubmed: 30796256
doi: 10.1038/s41598-019-39000-z
pii: 10.1038/s41598-019-39000-z
pmc: PMC6384912
doi:
Substances chimiques
Inositol Phosphates
0
Ligands
0
Receptor, Serotonin, 5-HT2C
0
Receptors, Adrenergic, alpha-2
0
Arachidonic Acid
27YG812J1I
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2557Références
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