Effects of salt on A2A adenosine receptors expression and function: in vitro approach and pathophysiological perspectives

Salt (sodium chloride) and A2A adenosine receptors (A2AR) have both been implicated in blood pressure regulation. While high salt consumption raises blood pressure, A2AR is a key mediator of coronary vasodilation. Although a sodium ion binding pocket has been identified in A2AR, the physiological link between salt and A2AR remains poorly investigated. Hereby, we explored how salt modulates its expression and function in vitro. Using Adonis, an IgM mouse monoclonal antibody against A2AR with agonist properties, or CGS21680, an organic agonist, we evaluated the effects of distinct sodium chloride concentrations (low = 120 mM and high = 194 mM, compared to control = 133 mM) on A2AR protein expression, ligand binding affinity (KD) and function (cAMP production and EC50). We used peripheral blood mononuclear cells, a cellular model mimicking the behavior of A2AR expressed in the cardiovascular system. After 24h salt supplementation in culture medium, high salt concentration is associated with A2AR increased expression (mean ± SD: +131% ± 25.63 compared with control, p