Combinations of a full and partial agonist: Experimental evidence of curved isoboles
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Combinations of a full and partial agonist: Experimental evidence of curved isoboles
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
<a href="/en/project/GJ20-14318Y" target="_blank" >GJ20-14318Y: Individual and mixture immunotoxicity of environmental contaminants</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology Letters
ISSN
0378-4274
e-ISSN
1879-3169
Volume of the periodical
350
Issue of the periodical within the volume
OCT 10 2021
Country of publishing house
IE - IRELAND
Number of pages
8
Pages from-to
22-29
UT code for WoS article
000691222600003
EID of the result in the Scopus database
2-s2.0-85109202859