Effects of sodium on A2A adenosine receptor expression and function: in cellulo approach and pathophysiological perspectives

The expression and function of G-protein coupled receptor is modulated by small molecules including sodium ion, acting at an allosteric site. Using Adonis, an Ig M monoclonal antibody against a linear epitope located in the second loop of the A 2A adenosine receptor (A 2A R) with agonist properties, we evaluate in cellulo the effects of different sodium ion concentrations on the expression and function of A 2A R of peripheral blood mononuclear cells (PBMC). We found that high sodium ion concentration is associated with an increase in A 2A R expression and a decrease in cAMP production evaluated by measuring the half-maximal cAMP production, (EC 50 ), in a dose-dependent manner. When Adonis and sodium ions were added simultaneously in the culture medium, (competitive conditions), the K D and the EC 50 were high compared to non-competitive conditions (mean 27 and 3 folds respectively). These results suggest that sodium ions could promote Adonis binding to A 2A R as well as its activation. We hypothesize that, by steric hindrance, the binding of Adonis to A 2A R extends beyond the orthostatic site and prevents sodium ion from reaching its allosteric pocket. When sodium ion can reach its site, it acts as an allosteric modulator with respect to A 2A R expression and function. Because the action of sodium ions and A 2A -R have opposite effects on blood pressure, our results highlight a possible role of A 2A -R/sodium ions interaction in the regulation of blood pressure.