In 2013, Cannavo and colleagues transfected the β1-Adrenergic Receptor (β1AR) and the Sphingosine-1-Phosphate Receptor 1 (S1PR1) into HEK 293 to evaluate the direct interaction between these two receptors: the treatment with the respective agonists isoproterenol and Sphingosine 1-phosphate highlighted the reciprocal regulation between the two receptors, mediated by the activation of G protein-coupled receptor kinase-2, and the beneficial effects of S1PR1 in the offsetting of injurious β1AR overstimulation in heart failure [9]. Here, ADRB1 is linked to heart failure.