Cardiovascular α1-adrenoceptor subtypes: functions and signaling

Abstract

α1-Adrenoceptors (α1AR) are G protein-coupled receptors and include α1A, α1B, and α1Dsubtypes corresponding to cloned α1a, α1b, and α1d, respectively. α1AR mediate several cardiovascular actions of sympathomimetic amines such as vasoconstriction and cardiac inotropy, hypertrophy, metabolism, and remodeling. α1AR subtypes are products of separate genes and differ in structure, G protein-coupling, tissue distribution, signaling, regulation, and functions. Both α1AAR and α1BAR mediate positive inotropic responses. On the other hand, cardiac hypertrophy is primarily mediated by α1AAR. The only demonstrated major function of α1DAR is vasoconstriction. α1AR are coupled to phospholipase C, phospholipase D, and phospholipase A2; they increase intracellular Ca2+and myofibrillar sensitivity to Ca2+and cause translocation of specific phosphokinase C isoforms to the particulate fraction. Cardiac hypertrophic responses to α1AR agonists might involve activation of phosphokinase C and mitogen-activated protein kinase via Gq. α1AR subtypes might interact with each other and with other receptors and signaling mechanisms.Key words: cardiac hypertrophy, inotropic responses, central α1-adrenoreceptors, arrythmias.