期刊
BIOCHEMICAL PHARMACOLOGY
卷 78, 期 12, 页码 1456-1463出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2009.07.012
关键词
Adenosine receptors; Dopamine receptors; Competition curves; Two-state dimer receptor model; Equilibrium dissociation constants; Cooperativity
资金
- Spanish Ministerio de Ciencia y Tecnologia [SAF2005-00170, SAF200800146, SAF2006-05481]
- Fundacio La Marato de TV3 [060110]
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 D-1 or adenosine A(2A) 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. (C) 2009 Published by Elsevier Inc.
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