View source for Adrenergic receptor

{{CMG}}

[[Image:Adrenaline.svg|thumb|150px|right|[[Epinephrine]]]]
[[Image:Noradrenaline.svg|thumb|right|140px|[[Norepinephrine]]]]
The '''adrenergic receptors''' (or '''adrenoceptors''') are a class of [[G protein-coupled receptor]]s that are targets of the [[catecholamine]]s. Adrenergic [[Receptor (biochemistry)|receptor]]s specifically bind their [[endogenous]] [[ligand]]s, the catecholamines [[adrenaline]] and [[noradrenaline]] (called [[epinephrine]] and [[norepinephrine]] in the [[United States]]), and are activated by these.

Many cells possess these receptors, and the binding of an [[agonist]] will generally cause a sympathetic response (ie the [[fight-or-flight response|fight-or-flight]] response). For instance, the [[heart rate]] will increase and the [[pupil]]s will dilate, energy will be mobilized, and blood flow diverted from other organs to [[skeletal muscle]].(Note: Sympathetic activity will result in [[vasodilation]] of coronary arteries via the beta-2 adrenergic receptors.) 

==Subtypes==
[[Image:Adrenoceptor-Signal_transduktion.PNG|thumb|400px|left|The mechanism of adrenergic receptors. Adrenaline or noradrenaline are [[receptor ligands]] to either [[Alpha-1 adrenergic receptor|α<sub>1</sub>]], [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] or β-adrenergic receptors. [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] couples to [[Gq alpha subunit|G<sub>q</sub>]], which results in incerased intracellular [[calcium|Ca<sup>2+</sup>]] which results in e.g. [[smooth muscle]] contraction. [[Alpha-2 adrenergic receptor|α<sub>2</sub>]], on the other hand, couples to [[Gi alpha subunit|G<sub>i</sub>]], which causes a decrease of [[cyclic amp|cAMP]] activity, resulting in e.g. smooth muscle contraction. β receptors couple to [[Gs alpha subunit|G<sub>s</sub>]], and increases intracellular [[cyclic amp|cAMP]] activity, resulting in e.g. [[heart muscle]] contraction, smooth muscle relaxation and [[glycogenolysis]].]]
There are several types of adrenergic receptors, but there are two main groups: α-Adrenergic and β-Adrenergic.
* α receptors bind norepinephrine and epinephrine, though norepinephrine has higher affinity. [[Phenylephrine]] is a [[selective agonist]] of the α receptor. They exist as [[Alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptors]] and [[Alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptors]].
* β receptors are linked to [[G protein|G<sub>s</sub> proteins]], which in turn are linked to [[adenylyl cyclase]]. Agonist binding thus causes a rise in the intracellular concentration of the second messenger [[cyclic AMP|cAMP]]. Downstream effectors of cAMP include [[cAMP-dependent protein kinase]] (PKA), which mediates some of the intracellular events following hormone binding.

===Comparison===
{| border=1 cellspacing=0 cellpadding=5
|Receptor type
|Agonist potency order
| Selected action <BR> of [[agonist]]
| [[Second messenger system|Mechanism]]
| [[Adrenergic agonist|Agonists]]
| [[Adrenergic antagonist|Antagonists]]
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]]:<BR>{{Gene|ADRA1A}}, {{Gene|ADRA1B}}, {{Gene|ADRA1D}}
| noradrenaline≥ adrenaline >> [[isoprenaline]]
| [[smooth muscle]] contraction
| [[Gq alpha subunit|G<sub>q</sub>]]: [[phospholipase C]] (PLC) activated, [[inositol trisphosphate|IP<sub>3</sub>]] and [[calcium]] up 
| [[noradrenaline]]<BR>[[phenylephrine]]<BR>[[methoxamine]]<BR>[[Cirazoline]]
| ''([[Alpha blocker]]s)''<BR>[[phenoxybenzamine]]<BR>[[phentolamine]]<BR>[[prazosin]]<BR>[[tamsulosin]]<BR>[[terazosin]]
|- 
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]]:<BR>{{Gene|ADRA2A}}, {{Gene|ADRA2B}}, {{Gene|ADRA2C}}
| adrenaline > noradrenaline >> isoprenaline
| [[smooth muscle]] contraction
| [[Gi alpha subunit|G<sub>i</sub>]]: [[adenylate cyclase]] inactivated, [[Cyclic adenosine monophosphate|cAMP]] down
| [[clonidine]]<BR>[[lofexidine]]<BR>[[xylazine]]<BR>[[Tizanidine]]<BR>[[Guanfacine]]
| ''([[Alpha blocker]]s)''<BR>[[yohimbine]]
|- 
| β<sub>1</sub>:<BR>{{Gene|ADRB1}}
| isoprenaline > noradrenaline > adrenaline
| [[heart muscle]] contraction
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up
| [[noradrenaline]]<BR>[[isoprenaline]] <BR>[[dobutamine]]
| ''([[Beta blocker]]s)''<BR>[[metoprolol]]<BR>[[atenolol]]
|- 
| β<sub>2</sub>:<BR>ADRB2
| isoprenaline > adrenaline > noradrenaline 
| smooth muscle relaxation
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up
| ''([[Beta2-adrenergic receptor agonist|Short/long]])''<BR>[[salbutamol]] ([[albuterol]] in USA)<BR>[[bitolterol mesylate]]<BR>[[formoterol]]<BR>[[isoproterenol]]<BR>[[levalbuterol]]<BR>[[metaproterenol]]<BR>[[salmeterol]]<BR>[[terbutaline]]
| ''([[Beta blocker]]s)''<BR>[[butoxamine]]<BR>[[propranolol]]<BR>[[ritodrine]]
|- 
| β<sub>3</sub>:<BR>{{Gene|ADRB3}}
| isoprenaline > noradrenaline = adrenaline
| Enhance [[lipolysis]]
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up
| [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12324291&query_hl=2&itool=pubmed_docsum L-796568]<BR>CL 316,243<BR>LY 368842<BR>Ro 40-2148
| ''([[Beta blocker]]s)''<BR> [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8569714&dopt=Abstract SR 59230A]
|}

The absence of "ADRA1C" is intentional. At one time, there was a subtype known as C, but was found to be one of the previously discovered subtypes.  To avoid confusion, it was decided that there would never be a C subtype again and so if any new subtypes were discovered, naming would start with D.

===α receptors===
α receptors have several functions in common, but also individual effects. Common effects include:
* [[Vasoconstriction]] of [[arteries]] to [[kidney]] ([[renal artery]]), [[heart]] ([[coronary artery]]), [[viscera]], [[brain]], [[erectile tissue]] and [[salivary glands]].
* Vasoconstriction of [[veins]]
* Decrease motility of [[smooth muscle]] in [[gastrointestinal tract]]
* Contractions in male [[genitalia]] during [[ejaculation]]

====α<sub>1</sub> receptor====
{{Main|Alpha-1 adrenergic receptor}}
Specific actions of the α<sub>1</sub> receptor include:
*[[Vasoconstriction]] in [[blood vessels]] of [[skin]] & [[gastrointestinal system]]

*[[Smooth muscle]] contraction in:
**[[ureter]]
**[[hair]]s ([[arrector pili muscles]])
**[[uterus]] (when pregnant)
**[[urethral sphincter]]
**[[ureters]]
**[[bronchioles]] (although minor to the relaxing effect of β<sub>2</sub> receptor on bronchioles)

*[[urinary bladder]] contraction<ref name=purves> Neuroscience (Purves), Third Edition, table 20:2 </ref><ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=14634460&ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Excitatory alpha1-adrenergic receptors predominate over inhibitory beta-receptors in rabbit dorsal detrusor]: "alpha1-AR subtypes responsible for norepinephrine induced contraction of rabbit dorsal detrusor smooth muscle". Chou EC, Capello SA, Levin RM, Longhurst PA.</ref>

*[[Smooth muscle]] relaxation in:
**[[iris]]

*Positive ionotropic effect on [[heart muscle]]<ref name=purves/>. 

*Secretion from [[salivary gland]]<ref name=purves/>.

*Increase salivary [[potassium]] levels. 

*[[Glycogenolysis]] and [[gluconeogenesis]] from [[adipose tissue]] <ref name=purves/> and [[liver]].

*Secretion from [[sweat gland]]s <ref name=purves/>. 

*[[sodium|Na<sup>+</sup>]] reabsorption from [[kidney]]<ref name=purves/>.

====α<sub>2</sub> receptor==== <!--α2 receptor redrects here-->
Specific actions of the α<sub>2</sub> receptor include:

*Mediates [[synaptic transmission]] in pre- and postsynaptic [[synapse|nerve terminals]]. 

*Inhibition<ref>[http://www.jlr.org/cgi/content/abstract/22/8/1265 Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists] EE Wright and ER Simpson</ref> of [[lipolysis]] in [[adipose tissue]]<ref name=purves/>. 

*inhibition of [[insulin]] release in [[pancreas]]<ref name=purves/>. 
*induction of [[glucagon]] from pancreas.

*Aggregation of [[platelets]]

* contraction of [[sphincter]]s of the [[gastrointestinal tract]]

===β receptors===
As with α receptors, there are common actions of all β receptors, in addition to specific actions of each subtype. Common actions include:

* Stimulation of viscous, [[amylase]]-filldes secretions from [[salivary gland]]s.

====β<sub>1</sub> receptor==== <!--Beta-1 receptor redirects here-->
Specific actions of the β<sub>1</sub> receptor include:
*Increase [[cardiac output]]
**Increase [[heart rate]] <ref name=purves/> in [[sinoatrial node]] (SA node) (chronotropic effect)
**Increase [[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 conduction and [[cardiac muscle automaticity|automaticity]]<ref name=purves/> of [[atrioventricular node]] (AV node)

* [[Renin]] release from [[juxtaglomerular cells]]<ref name=purves/>. 

*[[Lipolysis]] in [[adipose tissue]]<ref name=purves/>. 

*Receptor also present in [[cerebral cortex]].

====β<sub>2</sub> receptor==== <!--Beta-2 receptor redirects here-->
Specific actions of the β<sub>2</sub> receptor include:

'''Muscular system'''
* [[Smooth muscle]] relaxation in [[uterus]] (when non-pregnant)<ref name=purves/>, [[GI tract]]<ref name=purves/>, [[blood vessels]]<ref name=purves/> and [[bronchi]]<ref name=purves/> (agonists can be useful in treating [[asthma]]) 
*Relax [[urinary sphincter]].
*Relax [[detrusor urinae muscle‎]] of [[Urinary bladder|bladder]] wall

'''Circulatory system'''
*Increase [[cardiac output]] (minor degree compared to β<sub>1</sub>.
**Increase [[heart rate]] <ref name=purves/> in [[sinoatrial node]] (SA node) (chronotropic effect)
**Increase [[heart atrium|atrial]] [[cardiac muscle]] contractility. (inotropic effect)
**Increases contractility and [[cardiac muscle automaticity|automaticity]]<ref name=purves/> of [[heart ventricle|ventricular]] cardiac muscle.

*Dilate [[hepatic artery]]

*Dilate [[arteries]] to [[skeletal muscle]]

'''digestive system'''
*[[Glycogenolysis]] and [[gluconeogenesis]] in liver<ref name=purves/>.

*[[Glycogenolysis]] and [[lactate]] release in [[skeletal muscle]]<ref name=purves/>.  

*Contract [[sphincters]] of [[GI tract]]

* [[Insulin]] secretion from [[pancreas]]<ref name=purves/><ref>[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8641318&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia.] Trovik TS, Vaartun A, Jorde R, Sager G.. Eur J Clin Pharmacol. 1995;48(5):327-32. PMID: 8641318</ref>  

* Thickened secretions from [[salivary gland]]s<ref name=purves/>.

'''Other'''

*Inhibit [[histamine]]-release from [[mast cells]] 

* Increase protein content of secretions from [[lacrimal gland]]s

*Increase [[renin]] secretion from [[kidney]] 

*Receptor also present in [[cerebellum]].

The 3D structure of β2-Adrenergic receptor has been determined [http://opm.phar.umich.edu/protein.php?search=2rh1].

====β<sub>3</sub> receptor==== <!--Beta-3 receptor redirects here-->
Specific actions of the β<sub>3</sub> receptor include:
Enhance [[lipolysis]] in [[adipose tissue]].

==Diagrams==
[[Image:G protein signal transduction (epinephrin pathway).png|thumb|400px|right|Epinephrine binds its receptor, that associates with an heterotrimeric G protein. The G protein associates with adenylate cyclase that converts ATP to cAMP, spreading the signal ([http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb58_1.html more details...])]]
{{-}}

== See also ==
*[[Beta adrenergic receptor kinase]]

== References ==
* {{cite book | first = | last =Rang HP, Dale MM, Ritter JM, Moore PK| authorlink = | coauthors = | year = 2003| month = | title =  Pharmacology | chapter = Ch. 11| editor = | others = | edition = | pages = | publisher = Elsevier Churchill Livingstone| location = | id = ISBN 0-443-07145-4| url = }}
* {{cite book | first = | last =Rang HP, Dale MM, Ritter JM, Flower RJ| authorlink = | coauthors = | year = 2007| month = | title =  Rang and Dale's Pharmacology | chapter = Ch. 11| editor = | others = | edition = | pages = 169-170 | publisher = Elsevier Churchill Livingstone| location = | id = ISBN 0-443-06911-5| url = }}
{{reflist|2}}

==External links==
*[http://macromoleculeinsights.com/adrenergic.php The Adrenergic Receptors]
*[http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1274 IUPHAR GPCR Database - Adrenoceptors]
*[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.890 Basic Neurochemistry: α- and β-Adrenergic Receptors]
*[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109691 Brief overview of functions of the beta-3 receptor]
*[http://cogprints.org/4095/ Theory of receptor activation]
*[http://cogprints.org/4093/ Desensitization of beta-1-receptors]
*{{UMichOPM|protein|pdbid|2rh1}} - 3D structure of beta-2 adrenergic receptor in membrane



{{Adrenergic Agonists}}
{{G protein-coupled receptors}}


[[Category:G protein coupled receptors]]

[[de:Adrenozeptor]]
[[fr:Récepteur adrénergique]]
[[ja:アドレナリン受容体]]
[[pl:Receptory adrenergiczne]]
[[pt:Receptores alfa]]
[[ru:Адренорецепторы]]
[[fi:Adrenerginen reseptori]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}