A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses
Burgueño, Javier (Laboratoris Esteve. Department of Pharmacology, Drug Discovery & Preclinical Development)
Pujol Argemí, Marta (Laboratoris Esteve. Department of Pharmacology, Drug Discovery & Preclinical Development)
Monroy, Xavier (Laboratoris Esteve. Department of Pharmacology, Drug Discovery & Preclinical Development)
Roche, David (Universitat Internacional de Catalunya. Facultat de Ciències Econòmiques i Socials)
Varela, Maria Jose (Universidade de Santiago de Compostela)
Merlos, Manuel (Laboratoris Esteve. Department of Pharmacology, Drug Discovery & Preclinical Development)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública

Date:	2017
Abstract:	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/K)), 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/K) 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.
Grants:	Ministerio de Economía y Competitividad 2013-018-C03-02 Ministerio de Economía y Competitividad SAF2014-58396-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 7 (november 2017) , ISSN 2045-2322

DOI: 10.1038/s41598-017-15258-z
PMID: 29133887

11 p, 1.8 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles