Received for publication November 9, 2005.
Revised January 25, 2006.
Accepted for publication February 23, 2006.

THE "TWO-STATE DIMER RECEPTOR MODEL". A GENERAL MODEL FOR RECEPTOR DIMERS

Abstract

Non-linear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Since there are clear evidences of receptor dimerization these non-linear 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 paper the performance of the model has been analyzed in fitting data from A₁ adenosine receptors agonist binding, which is 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" is similarly good than 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, which display concave upward Scatchard plots. 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 cannot 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

Key words: Adenosine, Dopamine, Histamine, G protein regulation, Thermodynamic and kinetic processes and modeling, Receptor binding studies

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