Cardiovascular alpha(1)-adrenoceptor subtypes: functions and signaling

alpha(1)-Adrenoceptors (alpha(1)AR) are G protein-coupled receptors and inc lude alpha(1A), alpha(1B), and alpha(1D) subtypes corresponding to cloned a lpha(1a), alpha(1b), and alpha(1d), respectively. alpha(1)AR mediate severa l cardiovascular actions of sympathomimetic amines such as vasoconstriction and cardiac inotropy, hypertrophy, metabolism, and remodeling. alpha(1)AR subtypes are products of separate genes and differ in structure, G protein- coupling, tissue distribution, signaling, regulation, and functions. Both a lpha(1A)AR and alpha(1B)AR mediate positive inotropic responses. On the oth er hand, cardiac hypertrophy is primarily mediated by alpha(1A)AR. The only demonstrated major function of alpha(1D)AR is vasoconstriction. alpha(1)AR are coupled to phospholipase C, phospholipase D, and phospholipase A(2); t hey increase intracellular Ca2+ and myofibrillar sensitivity to Ca2+ and ca use translocation of specific phosphokinase C isoforms to the particulate f raction. Cardiac hypertrophic responses to alpha(1)AR agonists might involv e activation of phosphokinase C and mitogen-activated protein kinase via G( q). alpha(1)AR subtypes might interact with each other and with other recep tors and signaling mechanisms.