Rahul Sharma (Editor)

Beta 2 adrenergic receptor

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Species
  
Human

Entrez
  
154

Human
  
Mouse

Ensembl
  
ENSG00000169252

Beta-2 adrenergic receptor

Aliases
  
ADRB2, ADRB2R, ADRBR, B2AR, BAR, BETA2AR, adrenoceptor beta 2

External IDs
  
OMIM: 109690 MGI: 87938 HomoloGene: 30948 GeneCards: ADRB2

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. (Citation needed)

Contents

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

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.

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.

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 Gs, 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
  • Increases cardiac output (minor degree compared to β1).
  • Increases heart rate in sinoatrial node (SA node) (chronotropic effect).
  • Increases atrial cardiac muscle contractility. (inotropic effect).
  • Increases contractility and automaticity 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.
  • Glycogenolysis and lactate release in skeletal muscle.
  • Contract sphincters of GI tract.
  • Thickened secretions from salivary glands.
  • 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

    • Antagonists

    (Beta blockers)

  • butoxamine*
  • First generation (non-selective) β-blockers
  • ICI-118,551

    • * denotes selective agonists to the receptor.

    Interactions

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

    References

    Beta-2 adrenergic receptor Wikipedia
    (Text) CC BY-SA


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