Cardiovascular α₁-adrenoceptor subtypes: functions and signaling

α 1 -Adrenoceptors (α 1 AR) are G protein-coupled receptors and include α 1A , α 1B , and α 1D subtypes corresponding to cloned α 1a , α 1b , and α 1d , respectively. α 1 AR mediate several cardiovascular actions of sympathomimetic amines such as vasoconstriction and cardiac inotropy, hypertrophy, metabolism, and remodeling. α 1 AR subtypes are products of separate genes and differ in structure, G protein-coupling, tissue distribution, signaling, regulation, and functions. Both α 1A AR and α 1B AR mediate positive inotropic responses. On the other hand, cardiac hypertrophy is primarily mediated by α 1A AR. The only demonstrated major function of α 1D AR is vasoconstriction. α 1 AR are coupled to phospholipase C, phospholipase D, and phospholipase A 2 ; they increase intracellular Ca 2+ and myofibrillar sensitivity to Ca 2+ and cause translocation of specific phosphokinase C isoforms to the particulate fraction. Cardiac hypertrophic responses to α 1 AR agonists might involve activation of phosphokinase C and mitogen-activated protein kinase via G q . α 1 AR subtypes might interact with each other and with other receptors and signaling mechanisms.