β2-Adrenoceptor Antibodies

The β₂-adrenoceptor (β₂AR), encoded by ADRB2, is a class A G protein-coupled receptor activated by the endogenous catecholamines adrenaline and noradrenaline, with adrenaline generally showing higher potency. The receptor primarily couples to Gs, stimulating adenylyl cyclase and increasing intracellular cAMP. It is expressed in airway and vascular smooth muscle, skeletal muscle, and several immune cell populations. In airway smooth muscle, β₂AR activation promotes relaxation and bronchodilation. Receptor signaling is regulated by phosphorylation mediated by protein kinase A and G protein-coupled receptor kinases (GRKs). Agonist-induced GRK phosphorylation promotes β-arrestin recruitment, which limits G protein signaling and facilitates receptor internalization. Internalized receptors can recycle to the cell surface, while prolonged agonist exposure can reduce receptor abundance and responsiveness. Short-acting agonists such as salbutamol and long-acting agonists such as formoterol and salmeterol are used clinically as bronchodilators in asthma and chronic obstructive pulmonary disease. Clinically used nonselective β-blockers, including propranolol and carvedilol, also antagonize β₂AR signaling. β2-adrenoceptor desensitization, β-arrestin recruitment and internalization are regulated by phosphorylation of serine261/serine262 (pS261/pS262-ß2) in the third intracellular loop and carboxyl-terminal serine355/serine356 (pS355/pS356-ß2) and threonine360/serine364 (pT360/pS364-ß2) residues. Agonist-induced phosphorylation of S261/S262 is predominantly mediated by PKA. Agonist-induced phosphorylation of S355/S356 is predominantly mediated by GRK5/6, whereas phosphorylation of T360/S364 is predominantly mediated by GRK2/3. This nomenclature refers to the human β2. For more information on β2-adrenoceptor pharmacology please refer to the IUPHAR database. For further reading refer to:

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Kobilka BK. Structural insights into adrenergic receptor function and pharmacology. Trends Pharmacol Sci. 2011 Apr;32(4):213-8. doi: 10.1016/j.tips.2011.02.005. Epub 2011 Mar 15. PMID: 21414670; PMCID: PMC3090711.

Benkel T, Zimmermann M, Zeiner J, Bravo S, Merten N, Lim VJY, Matthees ESF, Drube J, Miess-Tanneberg E, Malan D, Szpakowska M, Monteleone S, Grimes J, Koszegi Z, Lanoiselée Y, O'Brien S, Pavlaki N, Dobberstein N, Inoue A, Nikolaev V, Calebiro D, Chevigné A, Sasse P, Schulz S, Hoffmann C, Kolb P, Waldhoer M, Simon K, Gomeza J, Kostenis E. How Carvedilol activates β2-adrenoceptors. Nat Commun. 2022 Nov 19;13(1):7109. doi: 10.1038/s41467-022-34765-w. PMID: 36402762; PMCID: PMC9675828.

Burghi V, Paradis JS, Officer A, Adame-Garcia SR, Wu X, Matthees ESF, Barsi-Rhyne B, Ramms DJ, Clubb L, Acosta M, Tamayo P, Bouvier M, Inoue A, von Zastrow M, Hoffmann C, Gutkind JS. Gαs is dispensable for β-arrestin coupling but dictates GRK selectivity and is predominant for gene expression regulation by
β2-adrenergic receptor. J Biol Chem. 2023 Nov;299(11):105293. doi:10.1016/j.jbc.2023.105293. Epub 2023 Sep 27. PMID: 37774973; PMCID: PMC10641165.

Radoux-Mergault A, Oberhauser L, Aureli S, Gervasio FL, Stoeber M.Subcellular location defines GPCR signal transduction. Sci Adv. 2023 Apr 21;9(16):eadf6059. doi: 10.1126/sciadv.adf6059. Epub 2023 Apr 19. PMID: 37075112; PMCID: PMC10115417.