The beta-2 adrenergic receptor (ò<sub>2</sub> adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation through trimeric G<sub>s</sub> proteins, increases cAMP, and, via downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.
Robert Lefkowitz and Brian Kobilka's study of the beta-2 adrenergic receptor as a model system earned them the 2012 Nobel Prize in Chemistry "for studies of G-protein-coupled receptors".
The official symbol for the human gene encoding the ò<sub>2</sub> adrenoreceptor is ADRB2.
The gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity and type 2 diabetes.
The 3D crystallographic structure (see figure and links to the right) of the ò<sub>2</sub>-adrenergic receptor has been determined by making a fusion protein with lysozyme to increase the hydrophilic surface area of the protein for crystal contacts. An alternative method, involving production of a fusion protein with an agonist, supported lipid-bilayer co-crystallization and generation of a 3.5 àresolution structure.
The crystal structure of the ò<sub>2</sub>Adrenergic Receptor-G<sub>s</sub> protein complex was solved in 2011. The largest conformational changes in the ò2AR include a 14 àoutward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an alpha helical extension of the cytoplasmic end of TM5.
This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca<sub>V</sub>1.2. This receptor-channel complex is coupled to the G<sub>s</sub> G protein, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A, and counterbalancing phosphatase PP2A. Protein kinase A then goes on to phosphorylate (and thus inactivate) myosin light-chain kinase, which causes smooth muscle relaxation, accounting for the vasodilatory effects of beta 2 stimulation. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.
Beta-2 adrenergic receptors have also been found to couple with G<sub>i</sub>, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 adrenergic receptors are coupled only to G<sub>s</sub>, and stimulation of these results in a more diffuse cellular response. This appears to be mediated by cAMP induced PKA phosphorylation of the receptor. Interestingly, Beta-2 adrenergic receptor was observed to localize exclusively to the T-tubular network of adult cardiomyocytes, as opposed to Beta-1 adrenergic receptor, which is observed also on the outer plasma membrane of the cell
Activation of the ò<sub>2</sub> adrenoreceptor with long-acting agents such as oral clenbuterol and intravenously-infused albuterol results in skeletomuscular hypertrophy and anabolism. The comprehensive anabolic, lipolytic, and ergogenic effects of long-acting ò<sub>2</sub> agonists such as clenbuterol render them frequent targets as performance-enhancing drugs in athletes. Consequently, such agents are monitored for and generally banned by WADA (World Anti-Doping Agency) with limited permissible usage under therapeutic exemptions; clenbuterol and other ò<sub>2</sub> adrenergic agents remain banned not as a beta-agonist, but rather an anabolic agent. These effects are largely attractive within agricultural contexts insofar that ò<sub>2</sub> adrenergic agents have seen notable extra-label usage in food-producing animals and livestock. While many countries including the United States have prohibited extra-label usage in food-producing livestock, the practice is still observed in many countries.
In the normal eye, beta-2 stimulation by salbutamol increases intraocular pressure via net:
In glaucoma, drainage is reduced (open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol may be employed.
(Beta blockers)
<nowiki>*</nowiki> denotes selective antagonist to the receptor.
Beta-2 adrenergic receptor has been shown to interact with: