A two-state model for the kinetics of competitive radioligand binding

British Journal of Pharmacology
Dong GuoAdriaan P IJzerman

Abstract

Ligand-receptor binding kinetics is receiving increasing attention in the drug research community. The Motulsky and Mahan model, a one-state model, offers a method for measuring the binding kinetics of an unlabelled ligand, with the assumption that the labelled ligand has no preference while binding to distinct states or conformations of a drug target. As such, the one-state model is not applicable if the radioligand displays biphasic binding kinetics to the receptor. We extended the Motulsky and Mahan model to a two-state model, in which the kinetics of the unlabelled competitor binding to different receptor states (R1 and R2 ) can be measured. With this extended model, we determined the binding kinetics of unlabelled N-5'-ethylcarboxamidoadenosine (NECA), a representative agonist for the adenosine A1 receptor. Subsequently, an application of the model was exemplified by measuring the binding kinetics of other A1 receptor ligands. In addition, limitations of the model were investigated as well. The kinetic rate constants of unlabelled NECA were comparable with the results of kinetic radioligand binding assays in which [3 H]-NECA was used. The model was further validated by good correlation between simulated results and the exp...Continue Reading

References

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Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators

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Citations

Apr 27, 2020·British Journal of Pharmacology·Guang-Ming WangZhe Zhang

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Methods Mentioned

BETA
scraping
scintillation spectrometry
competition binding
scintillation proximity assay

Software Mentioned

Graphpad
Graphpad Prism

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