Beta-2 adrenergic receptor
Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). The beta-2 adrenergic receptor (β2 adrenoreceptor), also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that interacts with (binds) epinephrine, a hormone and neurotransmitter (ligand synonym, adrenaline) whose signaling, via a downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation. Unlike other adrenergic receptors, norepinephrine does not produce β2 receptor stimulation.
The official symbol for the human gene encoding the β2 adrenoreceptor is ADRB2.[1]
Contents
Gene
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.[2]
Structure
The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined[3][4][5] 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.[6]
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. 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.[7]
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.[8] This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.[9]
Function
Actions of the β2 receptor include:
Muscular system
Tissue/Effect | Function | |
---|---|---|
Smooth muscle relaxation in: |
inhibits labor | |
GI tract (decreases motility) | Delay digestion during fight-or-flight response | |
detrusor urinae muscle of bladder wall[10] This effect is stronger than the alpha-1 receptor effect of contraction. |
Delay need of micturition | |
seminal tract[11] | ||
bronchi[12] | Facilitate respiration (agonists can be useful in treating asthma) | |
|
Increase perfusion of target organs | needed during fight-or-flight |
striated muscle | Tremor[11] (via PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release) | |
Increased mass and contraction speed[11] | fight-or-flight | |
glycogenolysis[11] | provide glucose fuel | |
pancreas | Insulin secretion | increases uptake of glucose by muscle |
Circulatory system
- Heart muscle contraction
- Increase cardiac output (minor degree compared to β1).
- Increase heart rate [12] in sinoatrial node (SA node) (chronotropic effect).
- Increase atrial cardiac muscle contractility. (inotropic effect).
- Increases contractility and automaticity[12] of ventricular cardiac muscle.
- Dilate hepatic artery.
- Dilate arterioles to skeletal muscle.
Eye
In the normal eye, beta-2 stimulation by salbutamol increases intraocular pressure via net:
- Increase in production of aqueous humour by the ciliary process,
- Subsequent increased pressure-dependent uveoscleral outflow of humour, despite reduced drainage of humour via the Canal of Schlemm.
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.
Digestive system
- Glycogenolysis and gluconeogenesis in liver.[12]
- Glycogenolysis and lactate release in skeletal muscle.[12]
- Contract sphincters of GI tract.
- Thickened secretions from salivary glands.[12]
- Insulin secretion from pancreas
Other
- Inhibit histamine-release from mast cells.
- Increase protein content of secretions from lacrimal glands.
- Increase renin secretion from kidney.
- Receptor also present in cerebellum.
- Bronchiole dilation (targeted while treating asthma attacks)
- Involved in brain - immune - communication [14]
Agonists
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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)[15]
- 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
Antagonists
* denotes selective agonists to the receptor.
Interactions
Beta-2 adrenergic receptor has been shown to interact with:
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See also
References
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Further reading
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External links
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