Receptor partial agonism and method to express receptor partial activation with respect to novel Full Logistic Model of mixture toxicology

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10373081" target="_blank" >RIV/00216208:11310/18:10373081 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/18:00490187

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.tox.2017.10.012" target="_blank" >http://dx.doi.org/10.1016/j.tox.2017.10.012</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2017.10.012" target="_blank" >10.1016/j.tox.2017.10.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Receptor partial agonism and method to express receptor partial activation with respect to novel Full Logistic Model of mixture toxicology

Popis výsledku v původním jazyce

Living organisms interact with various chemical compounds via receptors, which is described by the receptor theory. The affinity of the biologically active compounds toward receptors and their ability to trigger a biological or toxic signal vary substantially. In this work, we describe a new insight into understanding of the mode of action of receptor partial agonists and the receptor theory using a Full Logistic Model (FLM) of mixture toxicology. We describe the hypothesis that the effect of a partial agonist can be mathematically described via separation of agonistic and antagonistic behavior of the partial agonist where the antagonistic effect is described as an action of the compound producing zero effect. In this way, a competitive antagonist can be considered as an agonist with zero effect. This idea is also placed into a context with classical concepts, e.g., Gaddum&apos;s equation. Using the assumption that competitive antagonists are agonists with no effect, equations describing the microscopic and macroscopic equilibrium connts have been derived. Accordingly, we show that the constants could be calculated from the measured partial agonistic dose-response curve. As a consequence, we provide a simple mathematical tool for comparison of dose-response curves of drugs according to their affinities and efficacies.

Název v anglickém jazyce

Receptor partial agonism and method to express receptor partial activation with respect to novel Full Logistic Model of mixture toxicology

Popis výsledku anglicky

Living organisms interact with various chemical compounds via receptors, which is described by the receptor theory. The affinity of the biologically active compounds toward receptors and their ability to trigger a biological or toxic signal vary substantially. In this work, we describe a new insight into understanding of the mode of action of receptor partial agonists and the receptor theory using a Full Logistic Model (FLM) of mixture toxicology. We describe the hypothesis that the effect of a partial agonist can be mathematically described via separation of agonistic and antagonistic behavior of the partial agonist where the antagonistic effect is described as an action of the compound producing zero effect. In this way, a competitive antagonist can be considered as an agonist with zero effect. This idea is also placed into a context with classical concepts, e.g., Gaddum&apos;s equation. Using the assumption that competitive antagonists are agonists with no effect, equations describing the microscopic and macroscopic equilibrium connts have been derived. Accordingly, we show that the constants could be calculated from the measured partial agonistic dose-response curve. As a consequence, we provide a simple mathematical tool for comparison of dose-response curves of drugs according to their affinities and efficacies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10511 - Environmental sciences (social aspects to be 5.7)

Projekt

<a href="/cs/project/GA15-02328S" target="_blank" >GA15-02328S: Organismy a mechanismy určující osud endokrinních disruptorů v životním prostředí</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

393

Číslo periodika v rámci svazku

January 2018

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

8

Strana od-do

26-33

Kód UT WoS článku

000423636200004

EID výsledku v databázi Scopus

2-s2.0-85033408223