Beta-2 adrenergic receptor

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. ==Structure==

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. ==Mechanism==

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 ==Function==

2 receptor include:--> Musculoskeletal system 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. Circulatory system • Heart muscle contraction • Increase cardiac output (minor degree compared to β1). • Increases heart rate ==Ligands==

Agonists ====Spasmolytics used in asthma and COPD==== • Short-acting β2 agonists (SABA) • bitolterol • fenoterol • hexoprenaline • isoprenaline (INN) or isoproterenol (USAN) • levosalbutamol (INN) or levalbuterol (USAN) • orciprenaline (INN) or metaproterenol (USAN) • pirbuterol • procaterol • salbutamol (INN) or albuterol (USAN) • terbutaline • Long-acting β2 agonists (LABA) • arformoterol (some consider it to be an ultra-LABA) • bambuterol • clenbuterol • formoterol • salmeterol • Ultra-long-acting β2 agonists (ultra-LABA) • carmoterol • indacaterol • milveterol (GSK 159797) • olodaterol • vilanterol (GSK 642444) ====Tocolytic agents==== • Short-acting β2 agonists (SABA) • fenoterol • hexoprenaline • isoxsuprine • ritodrine • salbutamol (INN) or albuterol (USAN) • terbutaline β2 agonists used for other purposes • zilpaterol Antagonists (Beta blockers) • butoxamine* PAM at intracellular binding site • Cellular swelling == Interactions ==

Beta-2 adrenergic receptor has been shown to interact with: • AKAP12, • OPRD1, • Grb2, • SNX27 and • SLC9A3R1. == See also ==