Editing Adrenergic receptor

{{Short description|Class of G protein-coupled receptors}}
[[Image:100-AdrenergicReceptors-2rh1.tif|thumb|250px|β<sub>2</sub> adrenoceptor ({{PDB|2rh1|}}) shown binding [[carazolol]] (yellow) on its [[extracellular]] site. β<sub>2</sub> stimulates cells to increase energy production and utilization. The membrane the receptor is bound to in cells is shown with a gray stripe.]]

The '''adrenergic receptors''' or '''adrenoceptors''' are a class of [[G protein-coupled receptor]]s that are targets of many [[catecholamine]]s like [[norepinephrine]] (noradrenaline) and [[epinephrine]] (adrenaline) produced by the body, but also many medications like [[beta blocker]]s, [[Beta-2 adrenergic receptor|beta-2 (β<sub>2</sub>) agonists]] and [[Alpha-2 adrenergic receptor|alpha-2 (α<sub>2</sub>) agonists]], which are used to treat [[high blood pressure]] and [[asthma]], for example.

Many [[List of distinct cell types in the adult human body|cells]] have these receptors, and the binding of a catecholamine to the receptor will generally stimulate the [[sympathetic nervous system]] (SNS). The SNS is responsible for the [[fight-or-flight response]], which is triggered by experiences such as [[exercise]] or [[fear]]-causing situations. This response [[Mydriasis|dilates pupils]], increases heart rate, mobilizes energy, and diverts blood flow from non-essential organs to [[skeletal muscle]]. These effects together tend to increase physical performance momentarily.

==History==
{{Main|History of catecholamine research}}

{{multiple image
| align = right
| direction = vertical
| width1 = 150
| image1 = Adrenalin - Adrenaline.svg
| caption1 = [[Epinephrine]]
| image2 = Noradrenalin - Noradrenaline.svg
| width2 = 130
| caption2 = [[Norepinephrine]]
}}

By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different effects on body tissues, depending on the conditions of stimulation (such as the presence or absence of some toxin). Over the first half of the 20th century, two main proposals were made to explain this phenomenon:

# There were (at least) two different types of neurotransmitters released from sympathetic nerve terminals, or
# There were (at least) two different types of detector mechanisms for a single neurotransmitter.

The first hypothesis was championed by [[Walter Bradford Cannon]] and [[Arturo Rosenblueth]],<ref>{{cite journal | vauthors = Cannon WB, Rosenbluth A | date= 31 May 1933| title = Studies On Conditions Of Activity In Endocrine Organs XXVI: Sympathin E and Sympathin I | journal = American Journal of Physiology | volume= 104 | issue = 3 | pages = 557–574 | doi= 10.1152/ajplegacy.1933.104.3.557}}</ref> who interpreted many experiments to then propose that there were two neurotransmitter substances, which they called sympathin E (for 'excitation') and sympathin I (for 'inhibition').

The second hypothesis found support from 1906 to 1913, when [[Henry Hallett Dale]] explored the effects of adrenaline (which he called adrenine at the time), injected into animals, on blood pressure.  Usually, adrenaline would increase the blood pressure of these animals. Although, if the animal had been exposed to [[ergot]]oxine, the blood pressure decreased.<ref>{{cite journal | vauthors = Dale HH | title = On some physiological actions of ergot | journal = The Journal of Physiology | volume = 34 | issue = 3 | pages = 163–206 | date = May 1906 | pmid = 16992821 | doi =  10.1113/jphysiol.1906.sp001148 | pmc=1465771}}</ref><ref>{{cite journal | vauthors = Dale HH | title = On the action of ergotoxine; with special reference to the existence of sympathetic vasodilators | journal = The Journal of Physiology | volume = 46 | issue = 3 | pages = 291–300 | date = Jun 1913 | pmid = 16993202 | doi = 10.1113/jphysiol.1913.sp001592 | pmc=1420444}}</ref> He proposed that the ergotoxine caused "selective paralysis of motor myoneural junctions" (i.e. those tending to increase the blood pressure) hence revealing that under normal conditions that there was a "mixed response", including a mechanism that would relax smooth muscle and cause a fall in blood pressure. This "mixed response", with the same compound causing either contraction or relaxation, was conceived of as the response of different types of junctions to the same compound.

This line of experiments were developed by several groups, including DT Marsh and colleagues,<ref>{{cite journal | vauthors = Marsh DT, Pelletier MH, Rose CA | title = The comparative pharmacology of the N-alkyl-arterenols | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 92 | issue = 2 | pages = 108–20 | date = Feb 1948 | pmid = 18903395 }}</ref> who in February 1948 showed that a series of compounds structurally related to adrenaline could also show either contracting or relaxing effects, depending on whether or not other toxins were present. This again supported the argument that the muscles had two different mechanisms by which they could respond to the same compound. In June of that year, [[Raymond Ahlquist]], Professor of Pharmacology at Medical College of Georgia, published a paper concerning adrenergic nervous transmission.<ref>{{cite journal | vauthors = Ahlquist RP | s2cid = 1518772 | title = A study of the adrenotropic receptors | journal = The American Journal of Physiology | volume = 153 | issue = 3 | pages = 586–600 | date = Jun 1948 | pmid = 18882199 | doi =  10.1152/ajplegacy.1948.153.3.586}}</ref> In it, he explicitly named the different responses as due to what he called α receptors and β receptors, and that the only sympathetic transmitter was adrenaline. While the latter conclusion was subsequently shown to be incorrect (it is now known to be noradrenaline), his receptor nomenclature and concept of ''two different types of detector mechanisms for a single neurotransmitter'', remains.  In 1954, he was able to incorporate his findings in a textbook, ''Drill's Pharmacology in Medicine'',<ref>{{cite book|last=Drill|first=Victor Alexander|name-list-style=vanc|date=1954|title=Pharmacology in medicine: a collaborative textbook|url=https://archive.org/details/pharmacologyinme00dril|url-access=registration|location=New York|publisher=McGraw-Hill}}</ref> and thereby promulgate the  role played by α and β receptor sites in the adrenaline/noradrenaline cellular mechanism. These concepts would revolutionise advances in pharmacotherapeutic research, allowing the selective design of specific molecules to target medical ailments rather than rely upon traditional research into the efficacy of pre-existing herbal medicines.

==Categories==
[[File:Adrenoreceptor Signal Transduction.png|thumb|400px|The mechanism of adrenoreceptors. 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-adrenoreceptors. The [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] couples to [[Gq alpha subunit|G<sub>q</sub>]], which results in increased intracellular [[calcium|Ca<sup>2+</sup>]] and subsequent [[smooth muscle]] contraction. The [[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 in neurotransmitter release, as well as a decrease of [[cyclic amp|cAMP]] activity resulting in smooth muscle contraction. The β receptor couples 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]].]]
The mechanism of adrenoreceptors. 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-adrenoreceptors. The [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] couples to [[Gq alpha subunit|G<sub>q</sub>]], which results in increased intracellular [[calcium|Ca<sup>2+</sup>]] and subsequent [[smooth muscle]] contraction. The [[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 in neurotransmitter release, as well as a decrease of [[cyclic amp|cAMP]] activity resulting in smooth muscle contraction. The β receptor couples 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 two main groups of adrenoreceptors, α and β, with 9 subtypes in total:
* α receptors are subdivided into [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] (a [[G protein|G<sub>q</sub>]] coupled receptor) and [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] (a G<sub>i</sub> coupled receptor)<ref name=":1" />
** α<sub>1</sub> has 3 subtypes: α<sub>1A</sub>, α<sub>1B</sub> and α<sub>1D</sub>{{efn|name=d}}
** α<sub>2</sub> has 3 subtypes: α<sub>2A</sub>, α<sub>2B</sub> and α<sub>2C</sub>
* β receptors are subdivided into [[Beta-1 adrenergic receptor|β<sub>1</sub>]], [[Beta-2 adrenergic receptor|β<sub>2</sub>]] and [[Beta-3 adrenergic receptor|β<sub>3</sub>]]. All 3 are coupled to [[Gs protein|G<sub>s</sub> proteins]], but β<sub>2</sub> and β<sub>3</sub> also couple to G<sub>i</sub><ref name=":1" />

G<sub>i</sub> and G<sub>s</sub> are linked to [[adenylyl cyclase]]. [[Agonist]] binding thus causes a rise in the intracellular concentration of the second messenger (G<sub>i</sub> inhibits the production of cAMP)  [[cyclic AMP|cAMP]]. Downstream effectors of cAMP include [[cAMP-dependent protein kinase]] (PKA), which mediates some of the intracellular events following hormone binding.

===Roles in circulation===
Epinephrine (adrenaline) reacts with both α- and β-adrenoreceptors, causing vasoconstriction and vasodilation, respectively. Although α receptors are less sensitive to epinephrine, when activated at pharmacologic doses, they override the vasodilation mediated by β-adrenoreceptors because there are more peripheral α<sub>1</sub> receptors than β-adrenoreceptors. The result is that high levels of circulating epinephrine cause vasoconstriction. However, the opposite is true in the coronary arteries, where β<sub>2</sub> response is greater than that of α<sub>1</sub>, resulting in overall dilation with increased sympathetic stimulation. At lower levels of circulating epinephrine (physiologic epinephrine secretion), β-adrenoreceptor stimulation dominates since epinephrine has a higher affinity for the β<sub>2</sub> adrenoreceptor than the α<sub>1</sub> adrenoreceptor, producing vasodilation followed by decrease of peripheral vascular resistance.<ref>{{Cite journal|last1=Zwieten|first1=Van|last2=A|first2=P.|date=1986|title=Interaction Between α and β-Adrenoceptor-Mediated Cardiovascular Effects|journal=Journal of Cardiovascular Pharmacology|language=en-US|volume=8|pages=S21-8|doi=10.1097/00005344-198608004-00004|pmid=2427848|issn=0160-2446|doi-access=free}}</ref>

===Subtypes===
Smooth muscle behavior is variable depending on anatomical location. Smooth muscle contraction/relaxation is generalized below.  One important note is the differential effects of increased cAMP in smooth muscle compared to cardiac muscle.  Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.
{| class="wikitable"
!  scope="col" style="width: 125px;" | Receptor
! scope="col" style="width: 125px;" | Agonist potency order
! scope="col" style="width: 125px;" | Agonist action
! scope="col" style="width: 125px;" | [[Second messenger system|Mechanism]]
! scope="col" style="width: 125px;" | [[Adrenergic agonist|Agonists]]
! scope="col" style="width: 125px;" | [[Adrenergic antagonist|Antagonists]]
|-

|  [[Alpha-1 adrenergic receptor|α<sub>1</sub>]]: [[Alpha-1A adrenergic receptor|A]], [[Alpha-1B adrenergic receptor|B]], [[Alpha-1D adrenergic receptor|D]]{{efn|name=d}}
|  [[Norepinephrine]] > [[epinephrine]] >> [[isoprenaline]]<ref name=":0">{{Cite book|title=Rang and Dale's pharmacology| vauthors = Rang HP, Ritter JM, Flower RJ, Henderson G|publisher=Elsevier|year=2016|isbn=9780702053627|edition=8th|location=United Kingdom|pages=179|oclc=903083639}}</ref>
|  [[Smooth muscle]] contraction, [[mydriasis]], [[vasoconstriction]] in the skin, mucosa and abdominal [[viscera]] & sphincter contraction of the [[GI tract]] and [[urinary bladder]]
|  [[Gq alpha subunit|G<sub>q</sub>]]: [[phospholipase C]] (PLC) activated, [[inositol trisphosphate|IP<sub>3</sub>]], and [[Diglyceride|DAG]], rise in [[calcium]]<ref name=":1">{{Cite book|title=The adrenergic receptors in the 21st century|last=Perez|first=Dianne M.|publisher=Humana Press|year=2006|isbn=978-1588294234|location=Totowa, New Jersey|pages=54, 129–134|lccn=2005008529|oclc=58729119}}</ref>
|
''([[Alpha-adrenergic agonist#.CE.B11 agonists|Alpha-1 agonists]])''
* [[Noradrenaline]]
* [[Phenylephrine]]
* [[Methoxamine]]
* [[Cirazoline]]
* [[Xylometazoline]]
* [[Midodrine]]
* [[Metaraminol]]
* [[Chloroethylclonidine]]
* Adrenoswitches ([[Photopharmacology|photoswitchable]] agonists)<ref name="PrischichGomila2020">{{cite journal|last1=Prischich|first1=Davia|last2=Gomila|first2=Alexandre M. J.|last3=Milla-Navarro|first3=Santiago|last4=Sangüesa|first4=Gemma|last5=Diez-Alarcia|first5=Rebeca|last6=Preda|first6=Beatrice|last7=Matera|first7=Carlo|last8=Batlle|first8=Montserrat|last9=Ramírez|first9=Laura|last10=Giralt|first10=Ernest|last11=Hernando|first11=Jordi|last12=Guasch|first12=Eduard|last13=Meana|first13=J. Javier|last14=de la Villa|first14=Pedro|last15=Gorostiza|first15=Pau|title=Adrenergic modulation with photochromic ligands|journal=Angewandte Chemie International Edition|year=2020|volume=60|issue=7|pages=3625–3631|issn=1433-7851|doi=10.1002/anie.202010553|pmid=33103317|hdl=2434/778579|hdl-access=free}}</ref>
| ''([[Alpha-1 blocker]]s)''
* [[Acepromazine]]
* [[Alfuzosin]]
* [[Doxazosin]]
* [[Phenoxybenzamine]]
* [[Phentolamine]]
* [[Prazosin]]
* [[Tamsulosin]]
* [[Terazosin]]
* [[Trazodone]]
''([[Tricyclic antidepressant|TCAs]])''
* [[Clomipramine]]
* [[Doxepin]]
* [[Trimipramine]]
* Typical and atypical antipsychotics
''[[Histamine H1 antagonist|Antihistamine]]s (H1 antagonists)''
* [[Hydroxyzine]]
|-
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]]: [[Alpha-2A adrenergic receptor|A]], [[Alpha-2B adrenergic receptor|B]], [[Alpha-2C adrenergic receptor|C]]
|[[Epinephrine]] = [[norepinephrine]] >> [[isoprenaline]]<ref name=":0" />
| [[Smooth muscle]] mixed effects,  norepinephrine (noradrenaline) inhibition, [[platelet]] activation
| [[Gi alpha subunit|G<sub>i</sub>]]: [[adenylate cyclase]] inactivated, [[Cyclic adenosine monophosphate|cAMP]] down<ref name=":1" />
|
''([[Alpha-adrenergic agonist#.CE.B12 agonists|Alpha-2 agonists]])''
* [[Agmatine]]
* [[Dexmedetomidine]]
* [[Medetomidine]]
* [[Romifidine]]
* [[Clonidine]]
* [[Chloroethylclonidine]]
* [[Brimonidine]]
* [[Detomidine]]
* [[Lofexidine]]
* [[Xylazine]]
* [[Tizanidine]]
* [[Guanfacine]]
* [[Amitraz]]
| ''([[Alpha-2 blocker]]s)''
* [[Phenoxybenzamine]]
* [[Phentolamine]]
* [[Yohimbine]]
* [[Idazoxan]]
* [[Atipamezole]]
* [[Trazodone]]
* Typical and atypical [[antipsychotic]]s
|-
| [[Beta-1 adrenergic receptor|β<sub>1</sub>]]
| [[Isoprenaline]] > [[epinephrine]] > [[norepinephrine]]<ref name=":0" />
| Positive [[chronotropic]], [[dromotropic]] and [[inotropic]] effects, increased [[amylase]] secretion
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up<ref name=":1" />
| ''([[beta-1 agonist|β<sub>1</sub>-adrenergic agonist]])''
* [[Dobutamine]]
* [[Isoprenaline]]
* [[Noradrenaline]]
| ''([[Beta blocker]]s)''
* [[Metoprolol]]
* [[Atenolol]]
* [[Bisoprolol]]
* [[Propranolol]]
* [[Timolol]]
* [[Nebivolol]]
* [[Vortioxetine]]
|-
| [[Beta-2 adrenergic receptor|β<sub>2</sub>]]
| [[Isoprenaline]] > [[epinephrine]] > [[norepinephrine]]<ref name=":0" />
| [[Smooth muscle]] relaxation ([[bronchodilation]] for example)
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up (also [[Gi alpha subunit|G<sub>i</sub>]], see [[Alpha-2 adrenergic receptor|α<sub>2</sub>]])<ref name=":1" />
| ''([[Beta2-adrenergic receptor agonist|β<sub>2</sub>-adrenergic agonist]])''
* [[Salbutamol]] (Albuterol in USA)
* [[Bitolterol mesylate]]
* [[Formoterol]]
* [[Isoprenaline]]
* [[Levalbuterol]]
* [[Metaproterenol]]
* [[Salmeterol]]
* [[Terbutaline]]
* [[Ritodrine]]
| ''([[Beta blocker]]s)''
* [[Butoxamine]]
* [[Timolol]]
* [[Propranolol]]
* [[ICI-118,551]]
* [[Paroxetine]]<ref>{{Cite journal|vauthors=Tesmer JJ et al|date=2012-09-21|title=Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility|journal=ACS Chemical Biology|volume=7|issue=11|pages=1830–1839|doi=10.1021/cb3003013|pmid=22882301|pmc=3500392|issn=1554-8929}}</ref>
|-
| [[Beta-3 adrenergic receptor|β<sub>3</sub>]]
| [[Isoprenaline]] > [[norepinephrine]] = [[epinephrine]]<ref name=":0" />
| Enhance [[lipolysis]], promotes relaxation of [[detrusor muscle]] in the [[bladder]]
| [[Gs alpha subunit|G<sub>s</sub>]]: [[adenylate cyclase]] activated, [[Cyclic adenosine monophosphate|cAMP]] up (also [[Gi alpha subunit|G<sub>i</sub>]], see [[Alpha-2 adrenergic receptor|α<sub>2</sub>]])<ref name=":1" />
| ''([[beta-3 agonist|β<sub>3</sub>-adrenergic agonist]])''
* L-796568<ref name="pmid8569714">{{cite journal|vauthors=Nisoli E, Tonello C, Landi M, Carruba MO|title=Functional studies of the first selective beta 3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes|journal=Molecular Pharmacology|volume=49|issue=1|pages=7–14|date=1996|pmid=8569714|url=http://molpharm.aspetjournals.org/cgi/content/abstract/49/1/7 }}</ref>
* [[Amibegron]]
* [[Solabegron]]
* [[Mirabegron]]
| ''([[Beta blocker]]s)''
* [[SR 59230A]]
|}

===α receptors===
α receptors have actions in common, but also individual effects. Common (or still receptor unspecified) actions include:
* [[vasoconstriction]]<ref name="pmid9280371">{{cite journal|vauthors=Elliott J|title=Alpha-adrenoceptors in equine digital veins: evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction|journal=Journal of Veterinary Pharmacology and Therapeutics|volume=20|issue=4|pages=308–17|date=1997|pmid=9280371|doi=10.1046/j.1365-2885.1997.00078.x}}</ref>
* decreased flow of [[smooth muscle]] in [[gastrointestinal tract]]<ref name="pmid2889649">{{cite journal|vauthors=Sagrada A, Fargeas MJ, Bueno L|title=Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat|journal=Gut|volume=28|issue=8|pages=955–9|date=1987|pmid=2889649|pmc=1433140|doi=10.1136/gut.28.8.955}}</ref>

Subtype unspecific α agonists (see actions above) can be used to treat [[rhinitis]] (they decrease [[mucus]] secretion). Subtype unspecific α antagonists can be used to treat [[pheochromocytoma]] (they decrease [[vasoconstriction]] caused by norepinephrine).<ref name=":1" />

====α<sub>1</sub> receptor====
{{Main|Alpha-1 adrenergic receptor}}
α<sub>1</sub>-adrenoreceptors are members of the G<sub>q</sub> protein-coupled receptor superfamily. Upon activation, a [[heterotrimeric G protein]], [[Gq alpha subunit|G<sub>q</sub>]], activates [[phospholipase C]] (PLC). The PLC cleaves [[phosphatidylinositol 4,5-bisphosphate]] (PIP<sub>2</sub>), which in turn causes an increase in [[inositol trisphosphate]] (IP<sub>3</sub>) and [[diacylglycerol]] (DAG). The former interacts with [[calcium channel]]s of [[Endoplasmic reticulum|endoplasmic]] and [[sarcoplasmic reticulum]], thus changing the calcium content in a cell. This triggers all other effects, including a prominent slow after depolarizing current (sADP) in neurons.<ref>{{cite journal | vauthors = Smith RS, Weitz CJ, Araneda RC | title = Excitatory actions of noradrenaline and metabotropic glutamate receptor activation in granule cells of the accessory olfactory bulb | journal = Journal of Neurophysiology | volume = 102 | issue = 2 | pages = 1103–14 | date = Aug 2009 | pmid = 19474170 | doi = 10.1152/jn.91093.2008 | pmc=2724365}}</ref>

Actions of the α<sub>1</sub> receptor mainly involve [[smooth muscle]] contraction. It causes [[vasoconstriction]] in many [[blood vessels]], including those of the [[skin]], [[gastrointestinal system]], [[kidney]] ([[renal artery]])<ref name="pmid6270306">{{cite journal|vauthors=Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA |title=Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations|journal=The Journal of Pharmacology and Experimental Therapeutics|volume=219|issue=2|pages=400–6|date=1981|pmid=6270306|url=http://jpet.aspetjournals.org/cgi/content/abstract/219/2/400 }}</ref> and [[brain]].<ref>[http://cim.ucdavis.edu/masters/sessions2002/session4_ica.doc Circulation & Lung Physiology I] {{Webarchive|url=https://web.archive.org/web/20110726230145/http://cim.ucdavis.edu/masters/sessions2002/session4_ica.doc |date=2011-07-26 }} M.A.S.T.E.R. Learning Program, UC Davis School of Medicine</ref> Other areas of smooth muscle contraction are:
* [[ureter]]
* [[vas deferens]]
* [[hair]] ([[arrector pili muscle]]s)
* [[uterus]] (when pregnant)
* [[urethral sphincter]]
* [[urothelium]] and [[lamina propria]]<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=2013|pmid=23200975|doi=10.1016/j.urology.2012.09.011}}</ref>
* [[bronchioles]] (although minor relative to the relaxing effect of β<sub>2</sub> receptor on bronchioles)
* blood vessels of ciliary body and (stimulation  of dilator pupillae muscles of iris causes [[mydriasis]])

Actions also include [[glycogenolysis]] and [[gluconeogenesis]] from [[adipose tissue]] and [[liver]]; secretion from [[sweat gland]]s and [[sodium|Na<sup>+</sup>]] reabsorption from [[kidney]].<ref name=purves/>

[[Α1 antagonist|α<sub>1</sub> antagonists]] can be used to treat:<ref name=":1" />
* [[hypertension]] – decrease blood pressure by decreasing peripheral [[vasoconstriction]]
* [[benign prostate hyperplasia]] – relax [[smooth muscles]] within the prostate thus easing urination

====α<sub>2</sub> receptor====
{{Main|Alpha-2 adrenergic receptor}}
The α<sub>2</sub> receptor couples to the G<sub>i/o</sub> protein.<ref name="pmid18434433">{{cite journal|vauthors=Qin K, Sethi PR, Lambert NA|date=2008|title=Abundance and stability of complexes containing inactive G protein-coupled receptors and G proteins|journal=FASEB Journal|volume=22|issue=8|pages=2920–7|doi=10.1096/fj.08-105775|doi-access=free |pmc=2493464|pmid=18434433}}</ref> It is a presynaptic receptor, causing [[negative feedback]] on, for example, norepinephrine (NE). When NE is released into the synapse, it feeds back on the α<sub>2</sub> receptor, causing less NE release from the presynaptic neuron. This decreases the effect of NE. There are also α<sub>2</sub> receptors on the nerve terminal membrane of the post-synaptic adrenergic neuron.

Actions of the α<sub>2</sub> receptor include:
* decreased [[insulin]] release from the [[pancreas]]<ref name=purves/>
* increased [[glucagon]] release from the pancreas
* contraction of [[sphincter]]s of the [[Gastrointestinal tract|GI-tract]]
* [[negative feedback]] in the neuronal synapses - presynaptic inhibition of norepinephrine release in [[Central nervous system|CNS]]
* increased [[platelet]] aggregation
* decreases peripheral vascular resistance

[[Α2 agonist|α<sub>2</sub> agonists]] (see actions above) can be used to treat:<ref name=":1" />
* [[hypertension]] – decrease blood pressure-raising actions of the [[sympathetic nervous system]]

[[alpha blocker|α<sub>2</sub> antagonists]] can be used to treat:<ref name=":1" />
* [[impotence]] – relax penile smooth muscles and ease blood flow
* [[Depression (mood)|depression]] – enhance mood by increasing [[norepinephrine]] secretion

===β receptors===
Subtype unspecific β agonists can be used to treat:<ref name=":1" />
* [[heart failure]] – increase cardiac output acutely in an emergency
* [[circulatory shock]] – increase cardiac output thus redistributing blood volume
* [[anaphylaxis]] – [[bronchodilation]]

Subtype unspecific β antagonists ([[beta blocker]]s) can be used to treat:<ref name=":1" />
* [[heart arrhythmia]] – decrease the output of [[sinus node]] thus stabilizing heart function
* [[coronary artery disease]] – reduce heart rate and hence increasing [[oxygen]] supply
* [[heart failure]] – prevent sudden death related to this condition,<ref name=":1" /> which is often caused by [[ischemia]]s or [[arrhythmia]]s<ref>{{cite journal | vauthors = Ørn S, Dickstein K |date=2002-04-01|title=How do heart failure patients die? |journal=European Heart Journal Supplements |volume=4|issue=Suppl D|pages=D59–D65|doi=10.1093/oxfordjournals.ehjsupp.a000770 |doi-access=free}}</ref>
* [[hyperthyroidism]] – reduce peripheral sympathetic hyper-responsiveness
* [[migraine]] – reduce number of attacks
* [[stage fright]] – reduce [[tachycardia]] and [[tremor]]
* [[glaucoma]] – reduce [[intraocular pressure]]

====β<sub>1</sub> receptor====
{{Main|Beta-1 adrenergic receptor}}
Actions of the β<sub>1</sub> receptor include:
* increase [[cardiac output]] by increasing heart rate (positive [[chronotropic]] effect), conduction velocity (positive [[dromotropic]] effect), stroke volume (by enhancing contractility – positive [[inotropic]] effect), and rate of relaxation of the myocardium, by increasing calcium ion sequestration rate (positive [[lusitropic]] effect), which aids in increasing heart rate
* increase [[renin]] secretion from [[juxtaglomerular cells]] of the kidney<ref name="KimBriggs2011">{{cite journal | vauthors = Kim SM, Briggs JP, Schnermann J | title = Convergence of major physiological stimuli for renin release on the Gs-alpha/cyclic adenosine monophosphate signaling pathway | journal = Clinical and Experimental Nephrology | volume = 16 | issue = 1 | pages = 17–24 | date = February 2012 | pmid = 22124804 | pmc = 3482793 | doi = 10.1007/s10157-011-0494-1 }}</ref>
* increase [[ghrelin]] secretion from the stomach<ref>{{cite journal | vauthors = Zhao TJ, Sakata I, Li RL, Liang G, Richardson JA, Brown MS, Goldstein JL, Zigman JM | title = Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 36 | pages = 15868–73 | date = Sep 2010 | pmid = 20713709 | pmc = 2936616 | doi = 10.1073/pnas.1011116107 | first8 = J. M. | last8 = Zigman | author7 = and others | display-authors = 6 | bibcode = 2010PNAS..10715868Z | doi-access = free }}</ref>

====β<sub>2</sub> receptor====
{{Main|Beta-2 adrenergic receptor}}Actions of the β<sub>2</sub> receptor include:
* [[smooth muscle]] relaxation throughout many areas of the body, e.g. in [[bronchi]] (bronchodilation, see [[salbutamol]]),<ref name="purves">{{cite book|title=Neuroscience|last1=Fitzpatrick|first1=David|last2=Purves|first2=Dale|last3=Augustine|first3=George|publisher=Sinauer|year=2004|isbn=978-0-87893-725-7|edition=3rd|location=Sunderland, Mass|chapter=Table 20:2 |name-list-style=vanc}}</ref> [[GI tract]] (decreased motility), veins (vasodilation of blood vessels), especially those to skeletal muscle (although this vasodilator effect of norepinephrine is relatively minor and overwhelmed by α adrenoceptor-mediated vasoconstriction)<ref>{{cite web|vauthors = Klabunde R|title=Adrenergic and Cholinergic Receptors in Blood Vessels|url=http://www.cvphysiology.com/Blood%20Pressure/BP010b.htm|website=Cardiovascular Physiology|access-date=5 May 2015}}</ref>
* [[lipolysis]] in [[adipose tissue]]<ref name="pmid9399946">{{cite journal|vauthors=Large V, Hellström L, Reynisdottir S, Lönnqvist F, Eriksson P, Lannfelt L, Arner P|title = Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function|journal=The Journal of Clinical Investigation|volume=100|issue=12|pages=3005–13|date=1997|pmid=9399946|pmc=508512|doi=10.1172/JCI119854|display-authors=3}}</ref>
* [[anabolism]] in [[skeletal muscle]]<ref name="pmid17068216">{{cite journal|vauthors=Kline WO, Panaro FJ, Yang H, Bodine SC|s2cid=14292004|title=Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol|journal=Journal of Applied Physiology|volume=102|issue=2|pages=740–7|date=2007|pmid=17068216|doi=10.1152/japplphysiol.00873.2006}}</ref><ref name="pmid18374884">{{cite journal|vauthors=Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum S|title=Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure|journal=The Journal of Heart and Lung Transplantation|volume=27|issue=4|pages=457–61|date=2008|pmid=18374884|doi=10.1016/j.healun.2008.01.013|display-authors=3}}</ref>
* uptake of potassium into cells<ref>{{Cite book|title=Basic & Clinical Pharmacology|publisher=MCGraw-Hill Education|year=2018|isbn=978-1-259-64115-2|location=United States of America|pages=148}}</ref>
* relax non-pregnant [[uterus]]
* relax [[detrusor urinae muscle]] of [[bladder]] wall
* dilate [[arteries]] to [[skeletal muscle]]
* [[glycogenolysis]] and [[gluconeogenesis]]
* stimulates [[insulin]] secretion<ref name="SantulliLombardi2012">{{cite journal | vauthors = Santulli G, Lombardi A, Sorriento D, Anastasio A, Del Giudice C, Formisano P, Béguinot F, Trimarco B, Miele C, Iaccarino G | title = Age-related impairment in insulin release: the essential role of β(2)-adrenergic receptor | journal = Diabetes | volume = 61 | issue = 3 | pages = 692–701 | date = March 2012 | pmid = 22315324 | pmc = 3282797 | doi = 10.2337/db11-1027 }}</ref>
* contract [[sphincters]] of [[GI tract]]
* thickened secretions from [[salivary gland]]s<ref name=purves/>
* inhibit [[histamine]]-release from [[mast cells]]
* 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 = December 2000 | pmid = 11121511 }}</ref>

[[Β2-agonist|β<sub>2</sub> agonists]] (see actions above) can be used to treat:<ref name=":1" />
* [[asthma]] and [[COPD]] – reduce bronchial smooth muscle contraction thus dilating the [[bronchus]]
* [[hyperkalemia]] – increase cellular [[potassium]] intake
* [[preterm birth]] – reduce [[uterine]] smooth muscle contractions<ref>{{cite journal | vauthors = Haas DM, Benjamin T, Sawyer R, Quinney SK | title = Short-term tocolytics for preterm delivery - current perspectives | journal = International Journal of Women's Health | volume = 6 | pages = 343–9 | date = 2014 | pmid = 24707187 | pmc = 3971910 | doi = 10.2147/IJWH.S44048 |doi-access=free }}</ref>

====β<sub>3</sub> receptor====
{{Main|Beta-3 adrenergic receptor}}
Actions of the β<sub>3</sub> receptor include:
* increase of [[lipolysis]] in [[adipose tissue]]
* relax the [[bladder]]

β<sub>3</sub> agonists could theoretically be used as [[weight-loss drug]]s, but are limited by the side effect of [[tremor]]s.

==See also==
* [[Beta adrenergic receptor kinase]]
* [[Beta adrenergic receptor kinase-2]]
* [[Acetylcholine receptor]] (Cholinergic receptor)
:* [[Nicotinic acetylcholine receptor]]
:* [[Muscarinic acetylcholine receptor]]

==Notes==
{{notelist|refs={{efn|name=d|There is no α<sub>1C</sub> receptor. There was a subtype known as C, but it was found to be identical to one of the previously discovered subtypes. To avoid confusion, naming was continued with the letter D. Before June 1995 α<sub>1A</sub> was named α<sub>1C</sub>. α<sub>1D</sub> was named α<sub>1A</sub>, α<sub>1D</sub> or α<sub>1A/D</sub>.<ref>{{cite journal | vauthors = Hieble JP, Bylund DB, Clarke DE, Eikenburg DC, Langer SZ, Lefkowitz RJ, Minneman KP, Ruffolo RR | title = International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors: consensus update | journal = Pharmacological Reviews | volume = 47 | issue = 2 | pages = 267–70 | date = June 1995 | pmid = 7568329 }}</ref>}}}}

==References==
{{Reflist}}

==Further reading==
{{refbegin}}
* {{cite book | vauthors =Rang HP, Dale MM, Ritter JM, Flower RJ| year = 2007| title =  Rang and Dale's Pharmacology | chapter = Chapter 11: Noradrenergic transmission  | edition =  6th | pages = 169–170 | publisher = Elsevier Churchill Livingstone| isbn = 978-0-443-06911-6}}
{{refend}}

==External links==
* [http://pharmacologycorner.com/alpha-receptors-1-2/ Alpha receptors illustrated]
* {{usurped|1=[https://web.archive.org/web/20071019032532/http://macromoleculeinsights.com/adrenergic.php The Adrenergic Receptors]}}
* [http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=4 Adrenoceptors - IUPHAR/BPS guide to pharmacology]
* [https://www.ncbi.nlm.nih.gov/books/NBK28138/ Basic Neurochemistry: α- and β-Adrenergic Receptors]
* [http://cogprints.org/4095/ Theory of receptor activation]
* [http://cogprints.org/4093/ Desensitization of β<sub>1</sub> receptors]

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

{{DEFAULTSORT:Adrenergic Receptor}}
[[Category:Adrenergic receptors| ]]
[[Category:G protein-coupled receptors]]