Alpha2-adrenergic receptors

alpha2-adrenergic receptors (α2-ARs) consist of three subtypes, α2A-, α2B-, and α2C-AR, which are encoded by three highly homologous genes. These receptors bind to endogenous ligands, epinephrine and norepinephrine, and are blocked by the antagonist yohimbine. All three subtypes of α2-ARs share the same signaling pathways through the Gi/o subfamily of heterotrimeric G proteins, but display distinct trafficking profiles. Both the α2A- and α2C- ARs are involved in suppression of catecholamine release from neuronal terminals. Studies using genetically manipulated mice reveal that central effects of α2-adrenergic ligands, such as the hypotensive, sedative, and antiepileptic effects, are primarily mediated by the α2A- subtype. Conversely, the vascular hypertensive effect of these drugs is achieved through the α2B- subtype. Genetic variations of α2-ARs have been linked with a number of disease states in human populations including hypertension and diabetes.