Novel insights in β-adrenergic receptor signaling

The adrenergic receptors (ARs) are G-protein-coupled receptors that in response to stimuli activate several intracellular signaling regulating key biologic functions and affecting several pathological conditions, mainly cardiovascular diseases (CV). Indeed, almost 40% of approved drugs for the treatment of CV are based on adrenergic receptors targeting. Their discovery dates back to the beginning of the XX century but only in the last decades ARs signaling, function and regulation have been clarified. Generally, ARs signal through the cellular membrane to cytoplasmic G proteins. Besides this canonic pathway, it has been shown that activated ARs bind β-arrestins initiating desensitization, endocytosis and β-arrestin-dependent signaling. Thus, ARs are able to activate intracellular signaling in two different manners (through G-protein or β-arrestin), a phenomenon called “biased signaling.” In the last decades great advances have been made that increased the knowledge of ARs functions and their role in pathological conditions. The translation of these findings to clinic will be helpful to increase the specificity of the treatments of cardiac and vascular pathologies.