RT Journal Article
SR Electronic
T1 The Two-State Dimer Receptor Model: A General Model for Receptor Dimers
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1905
OP 1912
DO 10.1124/mol.105.020685
VO 69
IS 6
A1 Rafael Franco
A1 Vicent Casadó
A1 Josefa Mallol
A1 Carla Ferrada
A1 Sergi Ferré
A1 Kjell Fuxe
A1 Antoni Cortés
A1 Francisco Ciruela
A1 Carmen Lluis
A1 Enric I. Canela
YR 2006
UL http://molpharm.aspetjournals.org/content/69/6/1905.abstract
AB Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the “two-state dimer receptor model” has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A1 adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D1 receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the “two-independent-site receptor model”, the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots