Subtype-specific α1- and β-adrenoceptor signaling in the heart

Recent studies of adrenoceptors have revealed subtype-specific signaling, promiscuous G-protein coupling, time-dependent switching of intracellular signaling pathways, intermolecular interactions within or between adrenoceptor subfamilies, and G-protein-independent signaling pathways. These findings have extended the classical linear paradigm of G-protein-coupled receptor signaling to a complex ‘signalome’ in which an individual adrenoceptor initiates multiple signaling pathways in a temporally and spatially regulated manner. In particular, persistent stimulation of β-adrenoceptor subtypes causes a time-dependent switch of signaling pathways and elicits different, even opposing, functional roles of these receptors in regulating cardiac structure and function. Recent progress in the understanding of subtype-specific functions and signaling mechanisms of cardiac adrenoceptor subtypes, particularly β1-adrenoceptors, β2-adrenoceptors, α1A-adrenoceptors and α1B-adrenoceptors, might have important pathogenic and therapeutic implications for heart disease.