Combinations of a full and partial agonist: Experimental evidence of curved isoboles

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F21%3A00547233" target="_blank" >RIV/61388971:_____/21:00547233 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378427421001685?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378427421001685?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2021.06.016" target="_blank" >10.1016/j.toxlet.2021.06.016</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Combinations of a full and partial agonist: Experimental evidence of curved isoboles

Popis výsledku v původním jazyce

Concentration addition as a classic null model for toxicology and pharmacology is based on Loewe's mathematical formulation and the linearity of the isoboles. Novel mathematical models, however, propose curved isoboles in certain conditions. This article aims to test the hypothesis of the curvature of isoboles in experimental measurements. With the assumption of linear isoboles, a partial agonist acts as an antagonist above its maximal effect level. The isoboles automatically convert to a positive slope. For curved isoboles, a partial agonist acts as an antagonist at higher effect levels than its maximal effect alone. The discrepancies between effect levels were studied with an estrogen receptor binding assay (BMAEREluc/ER alpha) using a mixture of 17 beta-estradiol and fulvestrant as a partial agonist. A mixture of 17 beta-estradiol and fulvestrant acts as a partial agonist and causes the diminishing of the effect level of 17 beta-estradiol at a significantly higher level than the maximal effect of their partial-agonistic dose-response curve. Measured, elevated effect levels were well predicted by the mathematical model. Nonlinear isoboles may change our understanding and definition of synergism or antagonism and prompt further attention in receptor theory. (c) 2021 Elsevier B.V. All rights reserved.

Název v anglickém jazyce

Combinations of a full and partial agonist: Experimental evidence of curved isoboles

Popis výsledku anglicky

Concentration addition as a classic null model for toxicology and pharmacology is based on Loewe's mathematical formulation and the linearity of the isoboles. Novel mathematical models, however, propose curved isoboles in certain conditions. This article aims to test the hypothesis of the curvature of isoboles in experimental measurements. With the assumption of linear isoboles, a partial agonist acts as an antagonist above its maximal effect level. The isoboles automatically convert to a positive slope. For curved isoboles, a partial agonist acts as an antagonist at higher effect levels than its maximal effect alone. The discrepancies between effect levels were studied with an estrogen receptor binding assay (BMAEREluc/ER alpha) using a mixture of 17 beta-estradiol and fulvestrant as a partial agonist. A mixture of 17 beta-estradiol and fulvestrant acts as a partial agonist and causes the diminishing of the effect level of 17 beta-estradiol at a significantly higher level than the maximal effect of their partial-agonistic dose-response curve. Measured, elevated effect levels were well predicted by the mathematical model. Nonlinear isoboles may change our understanding and definition of synergism or antagonism and prompt further attention in receptor theory. (c) 2021 Elsevier B.V. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GJ20-14318Y" target="_blank" >GJ20-14318Y: Individuální a směsná imunotoxicita environmentálních kontaminantů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

1879-3169

Svazek periodika

350

Číslo periodika v rámci svazku

OCT 10 2021

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

8

Strana od-do

22-29

Kód UT WoS článku

000691222600003

EID výsledku v databázi Scopus

2-s2.0-85109202859