The two-state dimer receptor model: a general model for receptor dimers.
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 A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) 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.
Franco
Rafael
R
Dept. Bioquimica i Biologia Molecular, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain. rfranco@ub.edu
Casadó
Vicent
V
Mallol
Josefa
J
Ferrada
Carla
C
Ferré
Sergi
S
Fuxe
Kjell
K
Cortés
Antoni
A
Ciruela
Francisco
F
Lluis
Carmen
C
Canela
Enric I
EI
D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D019281:Dimerization; D008958:Models, Molecular; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*
D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D017447:Receptors, Dopamine D1; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled