beta2adrenergic

The beta-2 adrenergic receptor, or β2-adrenergic receptor (β2-AR), is a member of the beta-adrenergic receptor family and a G protein-coupled receptor. It is encoded by the ADRB2 gene in humans and binds catecholamines, with epinephrine typically showing higher potency than norepinephrine at this receptor. Activation of β2-AR stimulates the Gs protein, leading to activation of adenylate cyclase, increased cyclic AMP (cAMP), and protein kinase A (PKA) activity.

β2-AR is widely expressed, with high levels in airway and other smooth muscles, including bronchial, vascular, and uterine smooth muscle, as well as in liver and adipose tissue. In smooth muscle, β2-AR activation causes relaxation and bronchodilation, while in other tissues it mediates metabolic effects such as glycogenolysis and lipolysis. It also modulates mediator release from various cells, including mast cells, contributing to anti-inflammatory and bronchodilatory effects.

Pharmacologically, β2-adrenergic agonists are used to treat obstructive airway diseases. Short-acting agents (SABAs) like albuterol (salbutamol) provide rapid relief, while long-acting agents (LABAs) such as salmeterol and formoterol are used for maintenance therapy. In obstetrics, β2 agonists have been used as tocolytics to suppress premature labor, though safety concerns limit their use. Adverse effects include tremor and tachycardia, and chronic use can lead to tachyphylaxis due to receptor desensitization mediated by GRKs and beta-arrestins. Nonselective beta-blockers can block β2-AR, potentially causing bronchospasm in susceptible individuals.

Genetic variation in ADRB2, including variants at positions Arg16Gly and Gln27Glu, can influence receptor regulation and patient responses to β2-adrenergic drugs, though clinical implications vary across studies.