|, ADRB2R, ADRBR, B2AR, BAR, BETA2AR, adrenoceptor beta 2|
The beta-2 adrenergic receptor (β2 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 Gs proteins, increased cAMP, and downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.
Robert J.Lefkowitz and Brian Kobilka studied beta 2 adrenergic receptor as a model system which rewarded them the 2012 Nobel Prize in Chemistry “for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein-coupled-receptors”.
The official symbol for the human gene encoding the β2 adrenoreceptor is ADRB2.
The ADRB2 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 β2-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 Å resolution structure.
The Crystal Structure of the β2Adrenergic Receptor-Gs protein complex was solved in 2011. The largest conformational changes in the β2AR include a 14 Å outward 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 CaV1.2. This receptor-channel complex is coupled to the Gs 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 Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 adrenergic receptors are coupled only to Gs, 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 
|Smooth muscle relaxation in:||GI tract (decreases motility)||Inhibition of digestion|
|Bronchi||Facilitation of respiration.|
|Detrusor urinae muscle of bladder wall This effect is stronger than the alpha-1 receptor effect of contraction.||Inhibition of need for micturition|
|Uterus||Inhibition of labor|
|Increased perfusion and vasodilation||Blood vessels and arteries to skeletal muscle including the smaller coronary arteries and hepatic artery||Facilitation of muscle contraction and motility|
|Increased mass and contraction speed||Striated muscle|
|Insulin and glucagon secretion||Pancreas||Increased blood glucose and uptake by skeletal muscle|
|Tremor||Motor nerve terminals. Tremor is mediated by PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release.|
The function facilitates the fight-or-flight response.
Activation of the β2 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 β2 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 β2 adrenergic agents remain banned not as a beta-agonist, but rather an anabolic agent. These effects are largely attractive within agricultural contexts insofar that β2 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-2 adrenergic receptor|
|Transduction mechanisms||Primary: Gs|
|Primary endogenous agonists||epinephrine, norepinephrine|
|Agonists||isoprenaline, salbutamol, salmeterol, others|
|Antagonists||carvedilol, propranolol, labetalol, others|
|Positive allosteric modulators||Zn2+ (low concentrations)|
|Negative allosteric modulators||Zn2+ (high concentrations)|
Main article: Beta2-adrenergic agonist
* denotes selective antagonist to the receptor.
Beta-2 adrenergic receptor has been shown to interact with: