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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{{PBB_Summary
| section_title =
| summary_text =
}}


==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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Location (UCSC)n/an/a
PubMed searchn/an/a
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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.
  6. ↑ 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 (Nov 2007). "Crystal structure of the human beta2 adrenergic G-protein-coupled receptor". Nature. 450 (7168): 383–7. Bibcode:2007Natur.450..383R. doi:10.1038/nature06325. PMID 17952055.
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Further reading

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