Subtype-specific alpha1- and beta-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 beta-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 beta(1)-adrenoceptors, beta(2)-adrenoceptors, alpha(1A)-adrenoceptors and alpha(1B)-adrenoceptors, might have important pathogenic and therapeutic implications for heart disease.
Xiao
Rui-Ping
RP
Institute of Molecular Medicine, Peking University, Beijing 100871, China. xiaor@grc.nia.nih.gov
Zhu
Weizhong
W
Zheng
Ming
M
Cao
Chunmei
C
Zhang
Youyi
Y
Lakatta
Edward G
EG
Han
Qide
Q
D000818:Animals; D006801:Humans; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D020239:Receptor Cross-Talk; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2