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http://hdl.handle.net/2445/127978
Title: | Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist-antagonist binding modulation |
Author: | Casadó, Vicent Ferrada, Carla Bonaventura, Jordi Gracia, Eduard Mallol Montero, Josefa Canela Campos, Enric I. Lluís i Biset, Carme Cortés Tejedor, Antonio Franco Fernández, Rafael |
Keywords: | Bioquímica Biologia molecular Interacció cel·lular Biochemistry Molecular biology Cell interaction |
Issue Date: | 15-Dec-2009 |
Publisher: | Elsevier B.V. |
Abstract: | Many G-protein-coupled receptors (GPCRs) are expressed on the plasma membrane as dimers. Since drug binding data are currently fitted using equations developed for monomeric receptors, the interpretation of the pharmacological data are equivocal in many cases. As reported here, GPCR dimer models account for changes in competition curve shape as a function of the radioligand concentration used, something that cannot be explained by monomeric receptor models. Macroscopic equilibrium dissociation constants for the agonist and homotropic cooperativity index reflecting the intramolecular communication within the dopamine D1 or adenosine A2A receptor homodimer as well as hybrid equilibrium dissociation constant, which reflects the antagonist/agonist modulation may be calculated by fitting binding data from antagonist/agonist competition experiments to equations developed from dimer receptor models. Comparing fitting the data by assuming a classical monomeric receptor model or a dimer model, it is shown that dimer receptor models provide more clues useful in drug discovery than monomer-based models. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.bcp.2009.07.012 |
It is part of: | Biochemical Pharmacology, 2009, vol. 78, num. 12, p. 1456-1463 |
URI: | http://hdl.handle.net/2445/127978 |
Related resource: | https://doi.org/10.1016/j.bcp.2009.07.012 |
ISSN: | 0006-2952 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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