Beta-2 adrenergic receptor: Difference between revisions

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{{Infobox_gene}}
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The '''beta-2 adrenergic receptor''' (β<sub>2</sub> adrenoreceptor), also known as '''ADRB2''', is a cell membrane-spanning [[beta-adrenergic receptor]] that interacts with ([[ligand binding|binds]]) [[epinephrine]], a hormone and [[neurotransmitter]] (ligand synonym, [[adrenaline]]) whose signaling, via [[adenylate cyclase]] stimulation through trimeric Gs proteins, increased [[Cyclic adenosine monophosphate|cAMP]], and downstream [[L-type calcium channel]] interaction, mediates physiologic responses such as [[Beta2-adrenergic agonist|smooth muscle relaxation and bronchodilation]].<ref name="pmid16387578">{{cite journal | vauthors = Johnson M | title = Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation | journal = The Journal of Allergy and Clinical Immunology | volume = 117 | issue = 1 | pages = 18–24; quiz 25 | date = January 2006 | pmid = 16387578 | doi = 10.1016/j.jaci.2005.11.012 | doi-access = free }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}
 
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = 2RH1.png
| image_source = Crystallographic structure of the human β<sub>2</sub>-adrenergic G-protein coupled receptor ({{PDB|2RH1}}) depicted as a green cartoon structure and the bound partial inverse agonist [[carazolol]] ligand as spheres (carbon atom = grey, oxygen = red, nitrogen = blue).  The [[phospholipid]] [[lipid bilayer|bilayer]] is depicted as blue spheres (phosphate head groups) and yellow lines (lipid sidechains).<ref name="Cherezov_2007">{{cite journal | author = Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC | title = High-resolution crystal structure of an engineered human β<sub>2</sub>-adrenergic G protein-coupled receptor | journal = Science | volume = 318 | issue = 5854 | pages = 1258–65 | year = 2007 | pmid = 17962520 | doi = 10.1126/science.1150577 | issn = }}</ref><ref name="Rosenbaum_2007">{{cite journal | author = Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK | title = GPCR engineering yields high-resolution structural insights into β<sub>2</sub>-adrenergic receptor function | journal = Science | volume = 318 | issue = 5854 | pages = 1266–73 | year = 2007 | pmid = 17962519 | doi = 10.1126/science.1150609 | issn = }}</ref>
| PDB =
| Name = Adrenergic, beta-2-, receptor, surface
| HGNCid = 286
| Symbol = ADRB2
| AltSymbols =; ADRB2R; ADRBR; B2AR; BAR; BETA2AR
| OMIM = 109690
| ECnumber = 
| Homologene = 30948
| MGIid = 87938
| GeneAtlas_image1 = PBB_GE_ADRB2_206170_at_tn.png
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004941 |text = beta2-adrenergic receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0042803 |text = protein homodimerization activity}} {{GNF_GO|id=GO:0051380 |text = norepinephrine binding}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0005768 |text = endosome}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016324 |text = apical plasma membrane}} {{GNF_GO|id=GO:0043235 |text = receptor complex}}
| Process = {{GNF_GO|id=GO:0000187 |text = activation of MAPK activity}} {{GNF_GO|id=GO:0002024 |text = diet induced thermogenesis}} {{GNF_GO|id=GO:0002025 |text = norepinephrine-epinephrine vasodilation during regulation of blood pressure}} {{GNF_GO|id=GO:0002028 |text = regulation of sodium ion transport}} {{GNF_GO|id=GO:0002032 |text = arrestin mediated desensitization of G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0006898 |text = receptor-mediated endocytosis}} {{GNF_GO|id=GO:0007171 |text = transmembrane receptor protein tyrosine kinase activation (dimerization)}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007190 |text = adenylate cyclase activation}} {{GNF_GO|id=GO:0007243 |text = protein kinase cascade}} {{GNF_GO|id=GO:0008333 |text = endosome to lysosome transport}} {{GNF_GO|id=GO:0009409 |text = response to cold}} {{GNF_GO|id=GO:0030501 |text = positive regulation of bone mineralization}} {{GNF_GO|id=GO:0031649 |text = heat generation}} {{GNF_GO|id=GO:0040015 |text = negative regulation of body size}} {{GNF_GO|id=GO:0043410 |text = positive regulation of MAPKKK cascade}} {{GNF_GO|id=GO:0045453 |text = bone resorption}} {{GNF_GO|id=GO:0045944 |text = positive regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0045986 |text = negative regulation of smooth muscle contraction}} {{GNF_GO|id=GO:0050873 |text = brown fat cell differentiation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 154
    | Hs_Ensembl = ENSG00000169252
    | Hs_RefseqProtein = NP_000015
    | Hs_RefseqmRNA = NM_000024
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 148185001
    | Hs_GenLoc_end = 148188447
    | Hs_Uniprot = P07550
    | Mm_EntrezGene = 11555
    | Mm_Ensembl = ENSMUSG00000045730
    | Mm_RefseqmRNA = NM_007420
    | Mm_RefseqProtein = NP_031446
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 18
    | Mm_GenLoc_start = 62303865
    | Mm_GenLoc_end = 62305121
    | Mm_Uniprot = Q8BH38
  }}
}}
{{CMG}}


==Overview==
The official symbol for the human [[gene]] encoding the β<sub>2</sub> adrenoreceptor is ADRB2.<ref name="entrez">{{cite web | title = Entrez Gene: ADRB2 adrenoceptor beta 2, surface | url = https://www.ncbi.nlm.nih.gov/gene/154 | accessdate = 8 February 2015}}</ref>
The '''beta-2 adrenergic receptor''' (β<sub>2</sub> adrenoreceptor), also known as '''ADRB2''', is an [[beta-adrenergic receptor]], and also denotes the human [[gene]] encoding it.<ref name="entrez">{{cite web | title = Entrez Gene: ADRB1 adrenergic, beta-1-, receptor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=153| accessdate = }}</ref>
 
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==Gene==
==Gene==
The {{gene|ADRB2}} gene is [[intron]]less. Different polymorphic forms, [[point mutation]]s, and/or [[gene downregulation|downregulation]] of this gene are associated with nocturnal [[asthma]], [[obesity]] and [[type 2 diabetes]].<ref>{{cite web | title = Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=154| accessdate = }}</ref>
The {{gene|ADRB2}} gene is [[intron]]less. Different polymorphic forms, [[point mutation]]s, and/or [[gene downregulation|downregulation]] of this gene are associated with nocturnal [[asthma]], [[obesity]] and [[type 2 diabetes]].<ref>{{cite web | title = Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=154| accessdate = }}</ref>


==Structure==
==Structure==
The 3D crystallographic structure (see figure to the right) of the β<sub>2</sub>-adrenergic receptor has been determined ({{PDB|2R4R}}, {{PDB2|2R4S}}, {{PDB2|2RH1}}).<ref name="Rasmussen_2007">{{cite journal | author = Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK | title = Crystal structure of the human β<sub>2</sub>-adrenergic G-protein-coupled receptor | journal = Nature | volume = 450 | issue = 7168 | pages = 383–7 | year = 2007 | pmid = 17952055 | doi = 10.1038/nature06325 | issn = }}</ref><ref name="Cherezov_2007"/><ref name="Rosenbaum_2007"/>
The 3D crystallographic structure (see figure and links to the right) of the β<sub>2</sub>-adrenergic receptor has been determined<ref name="Cherezov_2007">{{cite journal |vauthors=Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC | title = High-resolution crystal structure of an engineered human β<sub>2</sub>-adrenergic G protein-coupled receptor | journal = Science | volume = 318 | issue = 5854 | pages = 1258–65 | year = 2007 | pmid = 17962520 | doi = 10.1126/science.1150577 | issn = | pmc=2583103| bibcode = 2007Sci...318.1258C }}</ref><ref name="Rosenbaum_2007">{{cite journal |vauthors=Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK | title = GPCR engineering yields high-resolution structural insights into β<sub>2</sub>-adrenergic receptor function | journal = Science | volume = 318 | issue = 5854 | pages = 1266–73 | year = 2007 | pmid = 17962519 | doi = 10.1126/science.1150609 | issn = | bibcode = 2007Sci...318.1266R }}</ref><ref name="Rasmussen_2007">{{cite journal | vauthors = Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK | title = Crystal structure of the human beta2 adrenergic G-protein-coupled receptor | journal = Nature | volume = 450 | issue = 7168 | pages = 383–7 | date = Nov 2007 | pmid = 17952055 | doi = 10.1038/nature06325 | bibcode = 2007Natur.450..383R }}</ref> 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.<ref>{{Cite journal|last=Liszewski|first=Kathy|date=1 October 2015|title=Dissecting the Structure of Membrane Proteins|url=http://www.genengnews.com/gen-articles/dissecting-the-structure-of-membrane-proteins/5583/|journal=[[Gen. Eng. Biotechnol. News|Genetic Engineering & Biotechnology News]]|volume=35|issue=17|page=16|type=paper}}{{subscription required}}</ref>


==Mechanism==
==Mechanism==
This receptor is directly associated with one of its ultimate effectors, the class C [[L-type calcium channel]] Ca<sub>V</sub>1.2. This receptor-channel complex also contains a [[G protein]] - [[Gs alpha subunit|G<sub>s</sub>]], which activate an [[adenylyl cyclase]], [[cAMP-dependent kinase]], and the counterbalancing [[phosphatase]], [[PP2A]]. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.<ref name="pmid16574446">{{cite journal | author = Rubenstein LA, Zauhar RJ, Lanzara RG | title = Molecular dynamics of a biophysical model for β<sub>2</sub>-adrenergic and G protein-coupled receptor activation | journal = J. Mol. Graph. Model. | volume = 25 | issue = 4 | pages = 396–409 | year = 2006 | pmid = 16574446 | doi = 10.1016/j.jmgm.2006.02.008 | issn = | url = http://www.bio-balance.com/JMGM_article.pdf }}</ref>
This receptor is directly associated with one of its ultimate effectors, the class C [[L-type calcium channel]] Ca<sub>V</sub>1.2. This receptor-channel complex is [[G protein-coupled receptor|coupled]] to the [[Gs alpha subunit|G<sub>s</sub>]] [[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.<ref name="pmid16574446">{{cite journal | vauthors = Rubenstein LA, Zauhar RJ, Lanzara RG | title = Molecular dynamics of a biophysical model for beta2-adrenergic and G protein-coupled receptor activation | journal = Journal of Molecular Graphics & Modelling | volume = 25 | issue = 4 | pages = 396–409 | date = Dec 2006 | pmid = 16574446 | doi = 10.1016/j.jmgm.2006.02.008 }}</ref>


==Function==
Beta-2 adrenergic receptors have also been found to couple with [[Gi alpha subunit|G<sub>i</sub>]], possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 adrenergic receptors are coupled only to G<sub>s</sub>, and stimulation of these results in a more diffuse cellular response.<ref name="pmid11053129">{{cite journal | vauthors = Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG | title = G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels | journal = Biophysical Journal | volume = 79 | issue = 5 | pages = 2547–56 | date = Nov 2000 | pmid = 11053129 | pmc = 1301137 | doi = 10.1016/S0006-3495(00)76495-2 | bibcode = 2000BpJ....79.2547C }}</ref> This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.<ref name="pmid12063255">{{cite journal | vauthors = Zamah AM, Delahunty M, Luttrell LM, Lefkowitz RJ | title = Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system | journal = The Journal of Biological Chemistry | volume = 277 | issue = 34 | pages = 31249–56 | date = Aug 2002 | pmid = 12063255 | doi = 10.1074/jbc.M202753200 }}</ref>
 
== Function ==
Actions of the β<sub>2</sub> receptor include:
Actions of the β<sub>2</sub> receptor include:


===Muscular system===
===Muscular System===
 
{{clear|right}}
{|class="wikitable"
{|class="wikitable"
!colspan=2| Effect
!Function
!Function
!Tissue
!Biological Role
|-
|-
|rowspan=5|
|rowspan=5|[[Smooth muscle]] relaxation in:
[[Smooth muscle]] relaxation in:
|
[[uterus]]
|
|-
| [[GI tract]] (decreases motility)
| [[GI tract]] (decreases motility)
| Delay [[digestion]] during [[fight-or-flight response]]
| style="background: LemonChiffon"| Inhibition of [[digestion]]
|-
|-
|
| [[Bronchi]]<ref name="purves">{{cite book | last1 = Fitzpatrick | first1 = David | last2 = Purves | first2 = Dale | last3 = Augustine | first3 = George | name-list-format = vanc | title = Neuroscience | publisher = Sinauer | location = Sunderland, Mass | year = 2004 | edition = Third | chapter = Table 20:2 | pages = | isbn = 0-87893-725-0 | oclc = | doi = }}</ref>  
[[detrusor urinae muscle‎]] of [[Urinary bladder|bladder]] wall<ref name="pmid7540086">{{cite journal | author = von Heyden B, Riemer RK, Nunes L, Brock GB, Lue TF, Tanagho EA | title = Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation | journal = Neurourol. Urodyn. | volume = 14 | issue = 2 | pages = 153–68 | year = 1995 | pmid = 7540086 | doi = 10.1002/nau.1930140208 | issn = }}</ref> This effect is stronger than the [[alpha-1 receptor]] effect of contraction.
| style="background: LemonChiffon"|  Facilitation of [[respiration (physiology)|respiration]]. Hence, beta-2 agonists can be useful in treating [[asthma]].
|Delay need of [[micturition]]
|-
|-
|[[seminal tract]]<ref name=Rang163> {{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 163 </ref>
|[[Detrusor urinae muscle]] of [[Urinary bladder|bladder]] wall<ref name="pmid7540086">{{cite journal | vauthors = von Heyden B, Riemer RK, Nunes L, Brock GB, Lue TF, Tanagho EA | title = Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation | journal = Neurourology and Urodynamics | volume = 14 | issue = 2 | pages = 153–68 | year = 1995 | pmid = 7540086 | doi = 10.1002/nau.1930140208 }}</ref><ref name="Moro et al. 2013">{{cite journal | vauthors = Moro C, Tajouri L, Chess-Williams R | title = Adrenoceptor function and expression in bladder urothelium and lamina propria | journal = Urology | volume = 81 | issue = 1 | pages = 211.e1–7 | date = January 2013 | pmid = 23200975 | doi = 10.1016/j.urology.2012.09.011 }}</ref> This effect is stronger than the [[alpha-1 receptor]] effect of contraction.
|
|Inhibition of need for [[micturition]]
|-
|-
| [[bronchi]]<ref name="purves">{{cite book | author = Fitzpatrick, David; Purves, Dale; Augustine, George | title = Neuroscience | publisher = Sinauer | location = Sunderland, Mass | year = 2004 | | edition = Third Edition | chapter =  Table 20:2 | pages = | isbn = 0-87893-725-0 | oclc = | doi = }}</ref>
|[[Uterus]]  
| Facilitate [[respiration]] (agonists can be useful in treating [[asthma]])
|Inhibition of labor
|-
|-
|[[Seminal tract]]<ref name=Rang163>{{cite book | vauthors = Rang HP |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 163</ref>
|
|
*[[blood vessels]]
**[[vasodilation|dilates]] smaller [[coronary arteries]]<ref name=Rang270>{{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=}} Page 270</ref>
**dilates [[hepatic artery]]
**[[arteries]] to [[skeletal muscle]]
| Increase perfusion of organs needed during fight-or-flight
|-
|-
|rowspan=3|[[striated muscle]]
| Increased [[perfusion]] and [[vasodilation]]
| Tremor<ref name=Rang163/> ||  
|[[Blood vessels]] and [[arteries]] to [[skeletal muscle]] including the smaller [[Right coronary artery|coronary arteries]]<ref name=Rang270>{{cite book | vauthors = Rang HP |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages= |isbn=0-443-07145-4 |oclc= |doi=| page = 270}}</ref> and [[hepatic artery proper|hepatic artery]]
|rowspan=2 style="background: lemonchiffon"|Facilitation of muscle contraction and motility
|-
|-
|Increased mass and contraction speed<ref name=Rang163/> || [[fight-or-flight]]
|Increased mass and contraction speed
|[[Striated muscle]]<ref name=Rang163/>  
|-
|-
|[[glycogenolysis]]<ref name=Rang163/> || provide [[glucose]] fuel
| [[Insulin]] and [[glucagon]] secretion
| Pancreas<ref>{{Cite journal|last=Philipson|first=L. H.|date=December 2002|title=beta-Agonists and metabolism|journal=The Journal of Allergy and Clinical Immunology|volume=110|issue=6 Suppl|pages=S313–317|issn=0091-6749|pmid=12464941|doi=10.1067/mai.2002.129702}}</ref>
|rowspan=2 style="background: LemonChiffon"| Increased blood [[glucose]] and uptake by skeletal muscle
|-
|-
|[[Glycogenolysis]]<ref name=Rang163/>
|
|-
| Tremor
|Motor nerve terminals.<ref name=Rang163/> Tremor is mediated by [[Protein kinase A|PKA]] mediated facilitation of presynaptic [[Ca2+|Ca<sup>2+</sup>]] influx leading to acetylcholine release.
||
|-
|}
{|
|style="vertical-align:top;width:360px;"|'''Legend '''
{{legend|LemonChiffon|The function facilitates the [[fight-or-flight response]].
}}
|}
|}


===Circulatory system===
===Circulatory system===
* Increase [[cardiac output]] (minor degree compared to β<sub>1</sub>).
* Heart muscle contraction
**Increase [[heart rate]] <ref name=purves/> in [[sinoatrial node]] (SA node) ([[chronotropic]] effect).
* increase [[cardiac output]] (minor degree compared to β<sub>1</sub>).
**Increase [[heart atrium|atrial]] [[cardiac muscle]] contractility. ([[inotropic]] effect).
**Increases [[heart rate]] <ref name=purves/> in [[sinoatrial node]] (SA node) ([[chronotropic]] effect).
**Increases [[heart atrium|atrial]] [[cardiac muscle]] contractility. ([[inotropic]] effect).
**Increases contractility and [[cardiac muscle automaticity|automaticity]]<ref name=purves/> of [[heart ventricle|ventricular]] cardiac muscle.
**Increases contractility and [[cardiac muscle automaticity|automaticity]]<ref name=purves/> of [[heart ventricle|ventricular]] cardiac muscle.
*Dilate [[hepatic artery]].
*Dilate [[hepatic artery proper|hepatic artery]].
*Dilate [[arteries]] to [[skeletal muscle]].
*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===
===Digestive system===
* [[Glycogenolysis]] and [[gluconeogenesis]] in liver.<ref name=purves/>
* [[Glycogenolysis]] and [[gluconeogenesis]] in liver.<ref name=purves/>
* [[Glycogenolysis]] and [[lactic acid|lactate]] release in [[skeletal muscle]].<ref name=purves/>
* [[Glycogenolysis]] and [[lactic acid|lactate]] release in [[skeletal muscle]].<ref name=purves/>
* Contract [[sphincters]] of [[GI tract]].
* Contract [[sphincters]] of [[Gastrointestinal tract]].
* [[Insulin]] secretion from [[pancreas]].<ref name=purves/><ref name="pmid8641318">{{cite journal | author = Trovik TS, Vaartun A, Jorde R, Sager G | title = Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia | journal = Eur. J. Clin. Pharmacol. | volume = 48 | issue = 5 | pages = 327–32 | year = 1995 | pmid = 8641318 | doi = | issn = }}</ref> 
* Thickened secretions from [[salivary gland]]s.<ref name=purves/>
* Thickened secretions from [[salivary gland]]s.<ref name=purves/>
*[[Insulin]] and [[glucagon]] secretion from pancreas. <ref>{{Cite journal|last=Philipson|first=L. H.|date=December 2002|title=beta-Agonists and metabolism|journal=The Journal of Allergy and Clinical Immunology|volume=110|issue=6 Suppl|pages=S313–317|issn=0091-6749|pmid=12464941|doi=10.1067/mai.2002.129702}}</ref>


===Other===
===Other===
* Inhibit [[histamine]]-release from [[mast cells]].
* Inhibit [[histamine]]-release from [[mast cells]].
* Increase protein content of secretions from [[lacrimal gland]]s.
* Increase protein content of secretions from [[lacrimal gland]]s.
* Increase [[renin]] secretion from [[kidney]].
* Receptor also present in [[cerebellum]].
* Receptor also present in [[cerebellum]].
* Bronchiole dilation (targeted while treating asthma attacks)
* Involved in brain - immune - communication <ref name="Elenkov">{{cite journal | vauthors = Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES | title = The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system | journal = Pharmacological Reviews | volume = 52 | issue = 4 | pages = 595–638  | date = Dec 2000 | pmid = 11121511 | doi =  }}</ref>


==Agonists==
==Agonists==
''([[Beta2-adrenergic receptor agonist|Short/long]])''
{{Infobox GPCR
*[[spasmolytic]]s in [[asthma]] and [[chronic obstructive pulmonary disease|COPD]]
| name                        = Beta-2 adrenergic receptor
**[[salbutamol]] ([[albuterol]] in USA)
| signal transduction        = Primary: [[Gs alpha subunit|G<sub>s</sub>]]<br />Secondary: [[Gi alpha subunit|G<sub>i/o</sub>]]
**[[bitolterol mesylate]]
| primary endogenous agonists = [[epinephrine]], [[norepinephrine]]
**[[isoproterenol]]
| agonists                    = [[isoprenaline]], [[salbutamol]], [[salmeterol]], [[Beta2-adrenergic agonist#Types|others]]
**[[levalbuterol]]
| antagonists                = [[carvedilol]], [[propranolol]], [[labetalol]], [[Beta blocker#Examples|others]]
**[[metaproterenol]]
| inverse agonists            = N/A
**[[salmeterol]]
| PAMs                        = [[zinc|Zn<sup>2+</sup>]] (low concentrations)
**[[terbutaline]]
| NAMs                        = [[zinc|Zn<sup>2+</sup>]] (high concentrations)
*[[ritodrine]] ([[tocolytic]])
| IUPHAR Target ID            = 29
| DrugBank Polypeptides ID    = P07550
| HMDB Protein ID            = HMDBP01634
}}
{{Main|Beta2-adrenergic agonist|l1=Beta<sub>2</sub>-adrenergic agonist}}
 
===Spasmolytics used in [[asthma]] and [[Chronic obstructive pulmonary disease|COPD]]===
* Short-acting β<sub>2</sub> agonists (SABA)
** [[bitolterol]]
** [[fenoterol]]
** [[hexoprenaline]]
** [[isoprenaline]] <small>([[International Nonproprietary Name|INN]])</small> or isoproterenol <small>([[United States Adopted Name|USAN]])</small>
** [[levosalbutamol]] <small>([[International Nonproprietary Name|INN]])</small> or levalbuterol <small>([[United States Adopted Name|USAN]])</small>
** [[orciprenaline]] <small>([[International Nonproprietary Name|INN]])</small> or metaproterenol <small>([[United States Adopted Name|USAN]])</small>
** [[pirbuterol]]
** [[procaterol]]
** [[salbutamol]] <small>([[International Nonproprietary Name|INN]])</small> or albuterol <small>([[United States Adopted Name|USAN]])</small>
** [[terbutaline]]
* Long-acting β<sub>2</sub> agonists (LABA)
** [[arformoterol]] (some consider it to be an ultra-LABA)<ref>{{cite journal | vauthors = Matera MG, Cazzola M | title = ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD? | journal = Drugs | volume = 67 | issue = 4 | pages = 503–15 | date = 2007 | pmid = 17352511 | doi = 10.2165/00003495-200767040-00002 }}</ref>
** [[bambuterol]]
** [[clenbuterol]]
** [[formoterol]]
** [[salmeterol]]
* Ultra-long-acting β<sub>2</sub> agonists (ultra-LABA)
** [[carmoterol]]
** [[indacaterol]]
** [[milveterol]] (GSK 159797)
** [[olodaterol]]
** [[vilanterol]] (GSK 642444)
 
===[[Tocolytic]] agents===
* Short-acting β<sub>2</sub> agonists (SABA)
** [[fenoterol]]
** [[hexoprenaline]]
** [[isoxsuprine]]
** [[ritodrine]]
** [[salbutamol]] <small>([[International Nonproprietary Name|INN]])</small> or albuterol <small>([[United States Adopted Name|USAN]])</small>
** [[terbutaline]]
 
===β<sub>2</sub> agonists used for other purposes===
* [[zilpaterol]]


==Antagonists==
==Antagonists==
''([[Beta blocker]]s)''
''([[Beta blocker]]s)''
*[[butoxamine]]*<ref name=Rang163/>
*[[butoxamine]]*<ref name=Rang163/>
*[[propranolol]] ([[antihypertensive]])
*[[Beta blocker#Nonselective agents|First generation (non-selective) β-blockers]]
*[[ICI-118,551]]*
*[[Propranolol]]
 
<nowiki>*</nowiki> denotes selective antagonist to the receptor.
 
== Interactions ==


<nowiki>*</nowiki> denotes [[selective agonist]]s to the receptor.
Beta-2 adrenergic receptor has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[AKAP12]],<ref name = pmid11309381>{{cite journal | vauthors = Fan G, Shumay E, Wang H, Malbon CC | title = The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization | journal = The Journal of Biological Chemistry | volume = 276 | issue = 26 | pages = 24005–14 | date = Jun 2001 | pmid = 11309381 | doi = 10.1074/jbc.M011199200 }}</ref><ref name = pmid9880537>{{cite journal | vauthors = Shih M, Lin F, Scott JD, Wang HY, Malbon CC | title = Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 3 | pages = 1588–95 | date = Jan 1999 | pmid = 9880537 | doi = 10.1074/jbc.274.3.1588 }}</ref>
* [[Delta Opioid receptor|OPRD1]],<ref name = pmid11278447>{{cite journal | vauthors = McVey M, Ramsay D, Kellett E, Rees S, Wilson S, Pope AJ, Milligan G | title = Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy | journal = The Journal of Biological Chemistry | volume = 276 | issue = 17 | pages = 14092–9 | date = Apr 2001 | pmid = 11278447 | doi = 10.1074/jbc.M008902200 }}</ref>
* [[Grb2]],<ref name = pmid9830057>{{cite journal | vauthors = Karoor V, Wang L, Wang HY, Malbon CC | title = Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 via tyrosine 350 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 49 | pages = 33035–41 | date = Dec 1998 | pmid = 9830057 | doi = 10.1074/jbc.273.49.33035 }}</ref>
* [[SNX27]]<ref name = pmid21602791>{{cite journal | vauthors = Temkin P, Lauffer B, Jäger S, Cimermancic P, Krogan NJ, von Zastrow M | title = SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors | journal = Nature Cell Biology | volume = 13 | issue = 6 | pages = 715–21 | date = Jun 2011 | pmid = 21602791 | pmc = 3113693 | doi = 10.1038/ncb2252 }}</ref> and
* [[Sodium-hydrogen antiporter 3 regulator 1|SLC9A3R1]].<ref name = pmid11882663>{{cite journal | vauthors = Karthikeyan S, Leung T, Ladias JA | title = Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors | journal = The Journal of Biological Chemistry | volume = 277 | issue = 21 | pages = 18973–8 | date = May 2002 | pmid = 11882663 | doi = 10.1074/jbc.M201507200 }}</ref><ref name = pmid9671706>{{cite journal | vauthors = Hall RA, Ostedgaard LS, Premont RT, Blitzer JT, Rahman N, Welsh MJ, Lefkowitz RJ | title = A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 15 | pages = 8496–501 | date = Jul 1998 | pmid = 9671706 | pmc = 21104 | doi = 10.1073/pnas.95.15.8496 |bibcode = 1998PNAS...95.8496H }}</ref><ref name = pmid9560162>{{cite journal | vauthors = Hall RA, Premont RT, Chow CW, Blitzer JT, Pitcher JA, Claing A, Stoffel RH, Barak LS, Shenolikar S, Weinman EJ, Grinstein S, Lefkowitz RJ | title = The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange | journal = Nature | volume = 392 | issue = 6676 | pages = 626–30 | date = Apr 1998 | pmid = 9560162 | doi = 10.1038/33458 |bibcode = 1998Natur.392..626H }}</ref>
{{Div col end}}


==Related Chapters==
== See also ==
*Other [[adrenergic receptors]]
*Other [[adrenergic receptors]]
**[[Alpha-1 adrenergic receptor]]
**[[Alpha-1 adrenergic receptor]]
**[[Alpha-2 adrenergic receptor]]
**[[Alpha-2 adrenergic receptor]]
**[[Beta-1 adrenergic receptor]]  
**[[Beta-1 adrenergic receptor]]
**[[Beta-3 adrenergic receptor]]
**[[Beta-3 adrenergic receptor]]
* [[Discovery and development of beta2 agonists]]


==References==
== References ==
{{Reflist|2}}
{{Reflist|32em}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin|32em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Frielle T, Caron MG, Lefkowitz RJ | title = Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning | journal = Clinical Chemistry | volume = 35 | issue = 5 | pages = 721–5  | date = May 1989 | pmid = 2541947 | doi =  }}
| citations =
* {{cite journal | vauthors = Taylor DR, Kennedy MA | title = Genetic variation of the beta(2)-adrenoceptor: its functional and clinical importance in bronchial asthma | journal = American Journal of Pharmacogenomics | volume = 1 | issue = 3 | pages = 165–74 | year = 2002 | pmid = 12083965 | doi = 10.2165/00129785-200101030-00002 }}
*{{cite journal | author=Frielle T, Caron MG, Lefkowitz RJ |title=Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning. |journal=Clin. Chem. |volume=35 |issue= 5 |pages= 721-5 |year= 1989 |pmid= 2541947 |doi=  }}
* {{cite journal | vauthors = Thibonnier M, Coles P, Thibonnier A, Shoham M | title = Molecular pharmacology and modeling of vasopressin receptors | journal = Progress in Brain Research | volume = 139 | issue =  | pages = 179–96 | year = 2002 | pmid = 12436935 | doi = 10.1016/S0079-6123(02)39016-2 }}
*{{cite journal | author=Taylor DR, Kennedy MA |title=Genetic variation of the beta(2)-adrenoceptor: its functional and clinical importance in bronchial asthma. |journal=American journal of pharmacogenomics : genomics-related research in drug development and clinical practice |volume=1 |issue= 3 |pages= 165-74 |year= 2002 |pmid= 12083965 |doi= }}
* {{cite journal | vauthors = Ge D, Huang J, He J, Li B, Duan X, Chen R, Gu D | title = beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese | journal = Annals of Human Genetics | volume = 69 | issue = Pt 1 | pages = 36–44  | date = Jan 2005 | pmid = 15638826 | doi = 10.1046/j.1529-8817.2003.00093.x }}
*{{cite journal | author=Thibonnier M, Coles P, Thibonnier A, Shoham M |title=Molecular pharmacology and modeling of vasopressin receptors. |journal=Prog. Brain Res. |volume=139 |issue=  |pages= 179-96 |year= 2002 |pmid= 12436935 |doi= }}
* {{cite journal | vauthors = Muszkat M | title = Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9 | journal = Clinical Pharmacology and Therapeutics | volume = 82 | issue = 2 | pages = 215–8  | date = Aug 2007 | pmid = 17329986 | doi = 10.1038/sj.clpt.6100142 }}
*{{cite journal | author=Ge D, Huang J, He J, ''et al.'' |title=beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese. |journal=Ann. Hum. Genet. |volume=69 |issue= Pt 1 |pages= 36-44 |year= 2005 |pmid= 15638826 |doi= 10.1046/j.1529-8817.2003.00093.x }}
* {{cite journal | vauthors = von Zastrow M, Kobilka BK | title = Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors | journal = The Journal of Biological Chemistry | volume = 267 | issue = 5 | pages = 3530–8  | date = Feb 1992 | pmid = 1371121 | doi =  }}
*{{cite journal | author=Muszkat M |title=Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9. |journal=Clin. Pharmacol. Ther. |volume=82 |issue= 2 |pages= 215-8 |year= 2007 |pmid= 17329986 |doi= 10.1038/sj.clpt.6100142 }}
* {{cite journal | vauthors = Gope R, Gope ML, Thorson A, Christensen M, Smyrk T, Chun M, Alvarez L, Wildrick DM, Boman BM | title = Genetic changes at the beta-2-adrenergic receptor locus on chromosome 5 in human colorectal carcinomas | journal = Anticancer Research | volume = 11 | issue = 6 | pages = 2047–50 | year = 1992 | pmid = 1663718 | doi =  }}
*{{cite journal | author=Bucens D, Pain MC |title=Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung. |journal=Circ. Res. |volume=37 |issue= 5 |pages= 588-96 |year= 1976 |pmid= 154 |doi=  }}
* {{cite journal | vauthors = Bouvier M, Guilbault N, Bonin H | title = Phorbol-ester-induced phosphorylation of the beta 2-adrenergic receptor decreases its coupling to Gs | journal = FEBS Letters | volume = 279 | issue = 2 | pages = 243–8  | date = Feb 1991 | pmid = 1848190 | doi = 10.1016/0014-5793(91)80159-Z }}
*{{cite journal | author=von Zastrow M, Kobilka BK |title=Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors. |journal=J. Biol. Chem. |volume=267 |issue= 5 |pages= 3530-8 |year= 1992 |pmid= 1371121 |doi=  }}
* {{cite journal | vauthors = Yang-Feng TL, Xue FY, Zhong WW, Cotecchia S, Frielle T, Caron MG, Lefkowitz RJ, Francke U | title = Chromosomal organization of adrenergic receptor genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 4 | pages = 1516–20  | date = Feb 1990 | pmid = 2154750 | pmc = 53506 | doi = 10.1073/pnas.87.4.1516 | bibcode = 1990PNAS...87.1516Y }}
*{{cite journal | author=Gope R, Gope ML, Thorson A, ''et al.'' |title=Genetic changes at the beta-2-adrenergic receptor locus on chromosome 5 in human colorectal carcinomas. |journal=Anticancer Res. |volume=11 |issue= 6 |pages= 2047-50 |year= 1992 |pmid= 1663718 |doi= }}
* {{cite journal | vauthors = Hui KK, Yu JL | title = Effects of protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, on beta-2 adrenergic receptor activation and desensitization in intact human lymphocytes | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 249 | issue = 2 | pages = 492–8  | date = May 1989 | pmid = 2470898 | doi =  }}
*{{cite journal | author=Bouvier M, Guilbault N, Bonin H |title=Phorbol-ester-induced phosphorylation of the beta 2-adrenergic receptor decreases its coupling to Gs. |journal=FEBS Lett. |volume=279 |issue= 2 |pages= 243-8 |year= 1991 |pmid= 1848190 |doi= }}
* {{cite journal | vauthors = Hen R, Axel R, Obici S | title = Activation of the beta 2-adrenergic receptor promotes growth and differentiation in thyroid cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 12 | pages = 4785–8  | date = Jun 1989 | pmid = 2471981 | pmc = 287358 | doi = 10.1073/pnas.86.12.4785 | bibcode = 1989PNAS...86.4785H }}
*{{cite journal  | author=Yang-Feng TL, Xue FY, Zhong WW, ''et al.'' |title=Chromosomal organization of adrenergic receptor genes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 4 |pages= 1516-20 |year= 1990 |pmid= 2154750 |doi= }}
* {{cite journal | vauthors = O'Dowd BF, Hnatowich M, Caron MG, Lefkowitz RJ, Bouvier M | title = Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor | journal = The Journal of Biological Chemistry | volume = 264 | issue = 13 | pages = 7564–9  | date = May 1989 | pmid = 2540197 | doi =  }}
*{{cite journal | author=Hui KK, Yu JL |title=Effects of protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, on beta-2 adrenergic receptor activation and desensitization in intact human lymphocytes. |journal=J. Pharmacol. Exp. Ther. |volume=249 |issue= 2 |pages= 492-8 |year= 1989 |pmid= 2470898 |doi= }}
* {{cite journal | vauthors = Bristow MR, Hershberger RE, Port JD, Minobe W, Rasmussen R | title = Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium | journal = Molecular Pharmacology | volume = 35 | issue = 3 | pages = 295–303  | date = Mar 1989 | pmid = 2564629 | doi =  }}
*{{cite journal  | author=Hen R, Axel R, Obici S |title=Activation of the beta 2-adrenergic receptor promotes growth and differentiation in thyroid cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 12 |pages= 4785-8 |year= 1989 |pmid= 2471981 |doi= }}
* {{cite journal | vauthors = Emorine LJ, Marullo S, Delavier-Klutchko C, Kaveri SV, Durieu-Trautmann O, Strosberg AD | title = Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 20 | pages = 6995–9  | date = Oct 1987 | pmid = 2823249 | pmc = 299215 | doi = 10.1073/pnas.84.20.6995 | bibcode = 1987PNAS...84.6995E }}
*{{cite journal  | author=O'Dowd BF, Hnatowich M, Caron MG, ''et al.'' |title=Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. |journal=J. Biol. Chem. |volume=264 |issue= 13 |pages= 7564-9 |year= 1989 |pmid= 2540197 |doi=  }}
* {{cite journal | vauthors = Chung FZ, Wang CD, Potter PC, Venter JC, Fraser CM | title = Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation | journal = The Journal of Biological Chemistry | volume = 263 | issue = 9 | pages = 4052–5  | date = Mar 1988 | pmid = 2831218 | doi =  }}
*{{cite journal | author=Bristow MR, Hershberger RE, Port JD, ''et al.'' |title=Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. |journal=Mol. Pharmacol. |volume=35 |issue= 3 |pages= 295-303 |year= 1989 |pmid= 2564629 |doi=  }}
* {{cite journal | vauthors = Yang SD, Fong YL, Benovic JL, Sibley DR, Caron MG, Lefkowitz RJ | title = Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2 | journal = The Journal of Biological Chemistry | volume = 263 | issue = 18 | pages = 8856–8  | date = Jun 1988 | pmid = 2837466 | doi =  }}
*{{cite journal | author=Emorine LJ, Marullo S, Delavier-Klutchko C, ''et al.'' |title=Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 20 |pages= 6995-9 |year= 1987 |pmid= 2823249 |doi= }}
* {{cite journal | vauthors = Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ | title = cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 1 | pages = 46–50  | date = Jan 1987 | pmid = 3025863 | pmc = 304138 | doi = 10.1073/pnas.84.1.46 | bibcode = 1987PNAS...84...46K }}
*{{cite journal | author=Chung FZ, Wang CD, Potter PC, ''et al.'' |title=Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation. |journal=J. Biol. Chem. |volume=263 |issue= 9 |pages= 4052-5 |year= 1988 |pmid= 2831218 |doi=  }}
* {{cite journal | vauthors = Chung FZ, Lentes KU, Gocayne J, Fitzgerald M, Robinson D, Kerlavage AR, Fraser CM, Venter JC | title = Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors | journal = FEBS Letters | volume = 211 | issue = 2 | pages = 200–6  | date = Jan 1987 | pmid = 3026848 | doi = 10.1016/0014-5793(87)81436-9 }}
*{{cite journal | author=Yang SD, Fong YL, Benovic JL, ''et al.'' |title=Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2. |journal=J. Biol. Chem. |volume=263 |issue= 18 |pages= 8856-8 |year= 1988 |pmid= 2837466 |doi=  }}
*{{cite journal | author=Kobilka BK, Dixon RA, Frielle T, ''et al.'' |title=cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 1 |pages= 46-50 |year= 1987 |pmid= 3025863 |doi= }}
*{{cite journal | author=Chung FZ, Lentes KU, Gocayne J, ''et al.'' |title=Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors. |journal=FEBS Lett. |volume=211 |issue= 2 |pages= 200-6 |year= 1987 |pmid= 3026848 |doi= }}
}}
{{refend}}
{{refend}}


{{membrane-protein-stub}}
== External links ==
{{G protein-coupled receptors}}
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2189 | title = &beta;<sub>2</sub>-adrenoceptor  | accessdate = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = }}
 
* {{UCSC gene info|ADRB2}}
[[Category:Adrenergic receptors‎]]
[[Category:G protein coupled receptors]]


[[Category:Drug]]
{{G protein-coupled receptors|g1}}


{{WH}}
[[Category:Adrenergic receptors]]
{{WS}}

Latest revision as of 17:12, 16 December 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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View/Edit Human

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 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.[1]

The official symbol for the human gene encoding the β2 adrenoreceptor is ADRB2.[2]

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.[3]

Structure

The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined[4][5][6] 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.[7]

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.[8]

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.[9] This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.[10]

Function

Actions of the β2 receptor include:

Muscular System

Function Tissue Biological Role
Smooth muscle relaxation in: GI tract (decreases motility) Inhibition of digestion
Bronchi[11] Facilitation of respiration. Hence, beta-2 agonists can be useful in treating asthma.
Detrusor urinae muscle of bladder wall[12][13] This effect is stronger than the alpha-1 receptor effect of contraction. Inhibition of need for micturition
Uterus Inhibition of labor
Seminal tract[14]
Increased perfusion and vasodilation Blood vessels and arteries to skeletal muscle including the smaller coronary arteries[15] and hepatic artery Facilitation of muscle contraction and motility
Increased mass and contraction speed Striated muscle[14]
Insulin and glucagon secretion Pancreas[16] Increased blood glucose and uptake by skeletal muscle
Glycogenolysis[14]
Tremor Motor nerve terminals.[14] Tremor is mediated by PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release.
Legend
  The function facilitates the fight-or-flight response.

Circulatory system

Eye

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.

Digestive system

Other

  • Inhibit histamine-release from mast cells.
  • Increase protein content of secretions from lacrimal glands.
  • Receptor also present in cerebellum.
  • Bronchiole dilation (targeted while treating asthma attacks)
  • Involved in brain - immune - communication [18]

Agonists

Beta-2 adrenergic receptor
Transduction mechanismsPrimary: Gs
Secondary: Gi/o
Primary endogenous agonistsepinephrine, norepinephrine
Agonistsisoprenaline, salbutamol, salmeterol, others
Antagonistscarvedilol, propranolol, labetalol, others
Inverse agonistsN/A
Positive allosteric modulatorsZn2+ (low concentrations)
Negative allosteric modulatorsZn2+ (high concentrations)
External resources
IUPHAR/BPS29
DrugBankP07550
HMDBHMDBP01634
Main article: Beta2-adrenergic agonist

Spasmolytics used in asthma and COPD

Tocolytic agents

β2 agonists used for other purposes

Antagonists

(Beta blockers)

* denotes selective antagonist to the receptor.

Interactions

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

See also

References

  1. ↑ Johnson M (January 2006). "Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation". The Journal of Allergy and Clinical Immunology. 117 (1): 18–24, quiz 25. doi:10.1016/j.jaci.2005.11.012. PMID 16387578.
  2. ↑ "Entrez Gene: ADRB2 adrenoceptor beta 2, surface". Retrieved 8 February 2015.
  3. ↑ "Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface".
  4. ↑ Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007). "High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor". Science. 318 (5854): 1258–65. Bibcode:2007Sci...318.1258C. doi:10.1126/science.1150577. PMC 2583103. PMID 17962520.
  5. ↑ Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007). "GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function". Science. 318 (5854): 1266–73. Bibcode:2007Sci...318.1266R. doi:10.1126/science.1150609. PMID 17962519.
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Further reading

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