The a1-adrenergic receptor (AR) family consists of three closely related gene products (a1A, a1B, and a1D) that mediate the actions of norepinephrine (NE) and epinephrine in sympathetically innervated tissues and brain. a1-ARs belong to the G protein-coupled receptor family and consist of single polypeptide chains predicted to have seven transmembrane spanning domains. With similar pharmacological and signaling properties, a1-AR subtypes act through Gq/11 proteins to activate phospholipase C, increase both inositol 1,4,5-trisphosphate production and intracellular Ca2+. Once activated by binding, a1-ARs initiate the cellular pathways leading to the regulation of physiological effects, including blood pressure maintenance, glucose metabolism, renal sodium reabsorption, and cardiac inotropy.