A critical re-evaluation of the slope factor of the operational model of agonism: When to exponentiate operational efficacy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F23%3A00579058" target="_blank" >RIV/67985823:_____/23:00579058 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1038/s41598-023-45004-7" target="_blank" >https://doi.org/10.1038/s41598-023-45004-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-023-45004-7" target="_blank" >10.1038/s41598-023-45004-7</a>

Result language

angličtina

Original language name

A critical re-evaluation of the slope factor of the operational model of agonism: When to exponentiate operational efficacy

Original language description

Agonist efficacy denoting the „strength“ of agonist action is a cornerstone in the proper assessment of agonist selectivity and signalling bias. The simulation models are very accurate but complex and hard to fit experimental data. The parsimonious operational model of agonism (OMA) has become successful in the determination of agonist efficacies and ranking them. In 1983, Black and Leff introduced the slope factor to the OMA to make it more flexible and allow for fitting steep as well as flat concentration-response curves. First, we performed a functional analysis to indicate the potential pitfalls of the OMA. Namely, exponentiation of operational efficacy may break relationships among the OMA parameters. The fitting of the Black & Leff equation to the theoretical curves of several models of functional responses and the experimental data confirmed the fickleness of the exponentiation of operational efficacy affecting estimates of operational efficacy as well as other OMA parameters. In contrast, fitting The OMA based on the Hill equation to the same data led to better estimates of model parameters. In conclusion, Hill equation-based OMA should be preferred over the Black & Leff equation when functional-response curves differ in the slope factor. Otherwise, the Black & Leff equation should be used with extreme caution acknowledging potential pitfalls.n

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

17587

UT code for WoS article

001087127100011

EID of the result in the Scopus database

2-s2.0-85174243286