Beta-2 Receptor
The bronchodilators used in asthma treatment target the beta-2 (β2) adrenergic receptor.
Mechanism of Action
Beta-2 agonists work by stimulating β2-adrenoceptors on airway smooth muscle, causing muscle relaxation and bronchodilation. 1 These receptors are widely distributed throughout the human bronchial tree, with the highest density found in alveolar regions. 1
Cellular Signaling Pathway
- β2-adrenoceptor stimulation triggers intracellular adenyl cyclase, which converts ATP to cyclic AMP (cAMP). 2
- Increased cAMP levels cause relaxation of bronchial smooth muscle and inhibit release of mediators from mast cells. 2
- β2-agonists also activate large-conductance Ca²⁺-activated K⁺ (KCa) channels via Gs protein, contributing to smooth muscle relaxation through membrane potential regulation. 3
Clinical Application in Asthma
Short-Acting Beta-2 Agonists (SABAs)
- Albuterol, levalbuterol, and pirbuterol are the treatment of choice for relief of acute asthma symptoms by targeting β2-receptors. 1
- SABAs provide rapid bronchodilation within minutes, with duration of 4-6 hours. 4
- These agents should be administered 5-20 minutes before exercise for prevention of exercise-induced bronchoconstriction. 1
Long-Acting Beta-2 Agonists (LABAs)
- Salmeterol and formoterol provide bronchodilation for at least 12 hours by stimulating the same β2-receptors. 1
- LABAs must always be combined with inhaled corticosteroids and never used as monotherapy for asthma. 1, 4
Receptor Selectivity
- Formoterol demonstrates more than 200-fold greater agonist activity at β2-receptors compared to β1-receptors. 2
- Although β2-receptors are predominant in bronchial smooth muscle, β1-receptors are predominant in the heart, which explains why selective β2-agonists are preferred for asthma treatment. 2
- The human heart contains 10-50% β2-receptors among total beta-adrenergic receptors, raising the possibility of cardiac effects even with highly selective β2-agonists. 2
Why Not Other Receptors?
- Alpha-1 and alpha-2 receptors are not targeted by primary asthma bronchodilators because they do not mediate bronchodilation. 1
- Beta-1 receptors are predominantly cardiac receptors and are not the primary target for asthma therapy. 2
- Anticholinergics (which inhibit muscarinic cholinergic receptors, not adrenergic receptors) provide additive benefit but are not first-line bronchodilators for asthma. 1