Alpha-adrenergic receptor (ADRA) (ADRA)

Alpha-adrenergic receptors are a major class of G protein-coupled receptors (GPCRs) that mediate the effects of the sympathetic nervous system by binding the catecholamines norepinephrine and epinephrine [StatPearls: Physiology, Adrenergic Receptors]. They are subdivided into alpha-1 (ADRA1) and alpha-2 (ADRA2) families, which possess distinct signaling mechanisms and physiological roles. Alpha-1 receptors are primarily coupled to Gq proteins, leading to increased intracellular calcium and smooth muscle contraction, which regulates vascular resistance and prostatic tone [IUPHAR: Alpha1-adrenoceptors]. In contrast, alpha-2 receptors are coupled to Gi proteins, inhibiting adenylyl cyclase and often acting as presynaptic autoreceptors to provide feedback inhibition of neurotransmitter release [IUPHAR: Alpha2-adrenoceptors]. Clinically, these receptors are targeted by a wide range of drugs: alpha-1 antagonists are used for hypertension and benign prostatic hyperplasia, while alpha-2 agonists are employed for conditions such as hypertension, glaucoma, and ADHD [StatPearls: Alpha-1 Antagonists; StatPearls: Alpha-2 Agonists]. Because alpha-1 and alpha-2 receptors often produce opposing physiological effects, non-selective agents must be used with caution regarding systemic side effects like orthostatic hypotension or reflex tachycardia.

Other names

Alpha-adrenoceptorAdrenoceptor alphaα-adrenergic receptor

Alpha-1 receptors (ADRA1) are Gq-coupled, activating phospholipase C to increase intracellular calcium, leading to smooth muscle contraction [StatPearls: Physiology, Adrenergic Receptors]. Alpha-2 receptors (ADRA2) are Gi-coupled, inhibiting adenylyl cyclase to decrease cAMP levels, which inhibits neurotransmitter release and modulates sympathetic outflow [StatPearls: Physiology, Adrenergic Receptors].