Applications and limitations of fitting of the operational model to determine relative efficacies of agonists

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00504453" target="_blank" >RIV/67985823:_____/19:00504453 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1038/s41598-019-40993-w" target="_blank" >https://doi.org/10.1038/s41598-019-40993-w</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-019-40993-w" target="_blank" >10.1038/s41598-019-40993-w</a>

Result language
angličtina
Original language name
Applications and limitations of fitting of the operational model to determine relative efficacies of agonists
Original language description
Proper determination of agonist efficacy is essential in the assessment of agonist selectivity and signalling bias. Agonist efficacy is a relative term that is dependent on the system in which it is measured, especially being dependent on receptor expression level. The operational model (OM) of functional receptor agonism is a useful means for the determination of agonist functional efficacy using the maximal response to agonist and ratio of agonist functional potency to its equilibrium dissociation constant (KA) at the active state of the receptor. However, the functional efficacy parameter tau is interdependent on two other parameters of OM, agonist's KA and the highest response that could be evoked in the system by any stimulus (EMAX). Thus, fitting of OM to functional response data is a tricky process. In this work we analyse pitfalls of fitting OM to experimental data and propose a rigorous fitting procedure where KA and EMAX are derived from half-efficient concentration of agonist and apparent maximal responses obtained from a series of functional response curves. Subsequently, OM with fixed KA and EMAX is fitted to functional response data to obtain tau.
Czech name
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Czech description
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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
30105 - Physiology (including cytology)

Project
<a href="/en/project/GA17-16182S" target="_blank" >GA17-16182S: Molecular basis of functional selectivity of Nsubstituted tetrahydropyridinium salts at muscarinic receptors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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