Beta-2 adrenergic receptor

The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning is_associated_with::beta-adrenergic receptor that interacts with (binds) is_associated_with::epinephrine a hormone and is_associated_with::neurotransmitter (ligand synonym, is_associated_with::adrenaline) whose signaling, via a downstream is_associated_with::L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.

The official symbol for the human is_associated_with::gene encoding the β2 adrenoreceptor is ADRB2.

Gene
The gene is is_associated_with::intronless. Different polymorphic forms, is_associated_with::point mutations, and/or downregulation of this gene are associated with nocturnal is_associated_with::asthma, is_associated_with::obesity and is_associated_with::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 is_associated_with::fusion protein with is_associated_with::lysozyme to increase the hydrophilic surface area of the protein for crystal contacts.

Mechanism
This receptor is directly associated with one of its ultimate effectors, the class C is_associated_with::L-type calcium channel CaV1.2. This receptor-channel complex is coupled to the Gs is_associated_with::G protein, which activates is_associated_with::adenylyl cyclase, catalysing the formation of is_associated_with::cyclic adenosine monophosphate (cAMP) which then activates is_associated_with::protein kinase A, and the counterbalancing is_associated_with::phosphatase is_associated_with::PP2A. 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.

Function
Actions of the β2 receptor include:

Circulatory system

 * Heart muscle contraction
 * Increase is_associated_with::cardiac output (minor degree compared to β1).
 * Increase is_associated_with::heart rate in is_associated_with::sinoatrial node (SA node) (is_associated_with::chronotropic effect).
 * Increase atrial is_associated_with::cardiac muscle contractility. (is_associated_with::inotropic effect).
 * Increases contractility and automaticity of ventricular cardiac muscle.
 * Dilate hepatic artery.
 * Dilate is_associated_with::arterioles to is_associated_with::skeletal muscle.

Eye
In the normal eye, beta-2 stimulation by is_associated_with::salbutamol increases intraocular pressure via net:
 * Increase in production of is_associated_with::aqueous humour by the is_associated_with::ciliary process,
 * Subsequent increased pressure-dependent uveoscleral outflow of humour, despite reduced drainage of humour via the is_associated_with::Canal of Schlemm.

In is_associated_with::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 is_associated_with::timolol may be employed.

Digestive system

 * is_associated_with::Glycogenolysis and is_associated_with::gluconeogenesis in liver.
 * is_associated_with::Glycogenolysis and lactate release in is_associated_with::skeletal muscle.
 * Contract is_associated_with::sphincters of is_associated_with::GI tract.
 * Thickened secretions from is_associated_with::salivary glands.
 * is_associated_with::Insulin secretion from pancreas

Other

 * Inhibit is_associated_with::histamine-release from is_associated_with::mast cells.
 * Increase protein content of secretions from is_associated_with::lacrimal glands.
 * Increase is_associated_with::renin secretion from is_associated_with::kidney.
 * Receptor also present in is_associated_with::cerebellum.
 * Bronchiole dilation (targeted while treating asthma attacks)
 * Involved in brain - immune - communication

Agonists

 * spasmolytics in is_associated_with::asthma and COPD


 * Short acting beta agonist (SABA)
 * is_associated_with::Salbutamol (albuterol in USA)
 * is_associated_with::Terbutaline
 * is_associated_with::Bitolterol mesylate
 * is_associated_with::Isoproterenol
 * is_associated_with::Levosalbutamol (levalbuteral in USA)
 * is_associated_with::Ritodrine (is_associated_with::tocolytic)
 * is_associated_with::Orciprenaline Sulfate / Metaproterenol


 * Long lasting beta agonist (LABA)
 * is_associated_with::Formoterol
 * is_associated_with::Salmeterol
 * is_associated_with::Clenbuterol


 * Ultra long lasting beta agonist (LABA)
 * is_associated_with::Arformeterol
 * is_associated_with::Carmoterol
 * is_associated_with::Indacaterol
 * GSK-159797, -597901, -159802, -642444 and -678007

Antagonists
(is_associated_with::Beta blockers)
 * is_associated_with::butoxamine*
 * First generation (non-selective) β-blockers
 * is_associated_with::ICI-118,551

* denotes is_associated_with::selective agonists to the receptor.

Interactions
Beta-2 adrenergic receptor has been shown to interact with:


 * is_associated_with::AKAP12,
 * OPRD1,
 * is_associated_with::Grb2,
 * is_associated_with::SNX27 and
 * SLC9A3R1.