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

Abstract

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 A2A adenosine receptor (A2AR) with agonist properties, we evaluate in cellulo the effects of different sodium ion concentrations on the expression and function of A2AR of peripheral blood mononuclear cells (PBMC). We found that high sodium ion concentration is associated with an increase in A2AR expression and a decrease in cAMP production evaluated by measuring the half-maximal cAMP production, (EC50), in a dose-dependent manner. When Adonis and sodium ions were added simultaneously in the culture medium, (competitive conditions), the KD and the EC50 were high compared to non-competitive conditions (mean 27 and 3 folds respectively). These results suggest that sodium ions could promote Adonis binding to A2AR as well as its activation. We hypothesize that, by steric hindrance, the binding of Adonis to A2AR 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 A2AR expression and function. Because the action of sodium ions and A2A-R have opposite effects on blood pressure, our results highlight a possible role of A2A-R/sodium ions interaction in the regulation of blood pressure.