Thermodynamic analysis in drug-receptor binding: the A3 adenosine receptor

This work deals with the study of the A3 adenosine receptors in the general scenario of all receptors studied so far from this point of view. Thermodynamic parameters, standard free energy (G°), standard enthalpy (H°) and standard entropy (S°) of the A3 adenosine receptor binding equilibrium are reported, discussed and compared with those observed for other membrane receptors. Moreover, available thermodynamic data of all G-protein coupled receptors (GPCRs) and ligand-gated ion channels receptors (LGICRs) are reported and discussed in terms of two important physical phenomena, the thermodynamic discrimination and enthalpy-entropy compensation. The enthalpy-entropy compensation phenomenon has been attributed for drug-receptor interactions to the solvent reorganization that accompanies the receptor binding process in diluted solutions. A thermodynamic data of A3 adenosine receptors will be compared with those obtained in different cell systems for A1, A2A and A2B receptors. It is clear that for A3 adenosine receptor agonist binding is entropy-driven but mostly enthalpy-driven for antagonists suggesting that agonists and antagonists are thermodynamically discriminated. The knowledge of the thermodynamic parameters could help the discovery and characterization of novel selective A3 agonists or antagonists.