A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses

Javier Burgueño, Marta Pujol, Xavier Monroy, David Roche, Maria Jose Varela, Manuel Merlos, Jesús Giraldo

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9 Citations (Scopus)

Abstract

© 2017 The Author(s). Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences. In this paper, we present a novel scale (log(τ)), that attempts to give extra substance to different compound profiles in order to better classify compounds and quantify their bias. The efficacy-driven log(τ) scale is not proposed as an alternative to the affinity&efficacy-driven log(τ/KA) scale but as a complement in those situations where partial agonism is present. Both theoretical and practical approaches using μ-opioid receptor agonists are presented.
Original languageEnglish
Article number15389
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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    Burgueño, J., Pujol, M., Monroy, X., Roche, D., Varela, M. J., Merlos, M., & Giraldo, J. (2017). A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses. Scientific Reports, 7(1), [15389]. https://doi.org/10.1038/s41598-017-15258-z