Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

Adrenergic receptor
From Wikipedia, the free encyclopedia

The adrenergic receptors (or adrenoceptors) are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). Although dopamine is a catecholamine, its receptors are in a different category. Many cells possess these receptors, and the binding of an agonist will generally cause a sympathetic (or sympathomimetic) response (e.g. the ght-or-ight response). For instance, the heart rate will increase and the pupils will dilate, energy will be mobilized, and blood ow diverted from other non-essential organs to skeletal muscle.

Epinephrine

Contents
Norepinephrine

1 Subtypes 1.1 Roles in circulation 1.2 Comparison 1.3 receptors 1.3.1 1 receptor 1.3.2 2 receptor 1.4 receptors 1.4.1 1 receptor 1.4.2 2 receptor 1.4.3 3 receptor 2 See also 3 References 4 Further reading 5 External links

Subtypes
There are two main groups of adrenergic receptors, and , with several subtypes.
1 of 10 12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

receptors have the subtypes 1 (a Gq coupled receptor) and 2 (a Gi coupled receptor). Phenylephrine is a selective agonist of the receptor. receptors have the subtypes 1, 2 and 3. All three are linked to Gs proteins (although 2 also couples to Gi),[1] which in turn are linked to adenylate cyclase. Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), which mediates some of the intracellular events following hormone binding. Isoprenaline is a selective agonist.

The mechanism of adrenergic receptors. Adrenaline or noradrenaline are receptor ligands to either 1, 2 or -adrenergic receptors. 1 couples to Gq, which results in increased intracellular Ca2+ which results in smooth muscle contraction. 2, on the other hand, couples

2 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

to Gi, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction. receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

Roles in circulation
Adrenaline (epinephrine) reacts with both - and -adrenoreceptors, causing vasoconstriction and vasodilation, respectively. Although receptors are less sensitive to epinephrine, when activated, they override the vasodilation mediated by -adrenoreceptors. The result is that high levels of circulating epinephrine cause vasoconstriction. At lower levels of circulating epinephrine, -adrenoreceptor stimulation dominates, producing an overall vasodilation.

Comparison
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. Selected action Mechanism of agonist

Receptor

Agonist potency order

Agonists

Antagonists (Alpha-1 blockers)

Gq: phospholipase C (PLC) 1: Smooth muscle Norepinephrine > epinephrine >> isoprenaline activated, contraction A, B, D IP3,and DAG, rise in calcium

(Alpha-1 agonists) Noradrenaline Phenylephrine Methoxamine Cirazoline Xylometazoline Midodrine

Alfuzosin Doxazosin Phenoxybenzamine Phentolamine Prazosin Tamsulosin Terazosin (TCA:s) Amitriptyline

3 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

Clomipramine Doxepin Trimipramine

(Alpha-2 agonists) Smooth muscle mixed effects and neurotransmitter Epinephrine norepinephrine >> isoprenaline inhibition & Cardiac muscle relaxation platelet activation Dexmedetomidine Medetomidine (Alpha-2 blockers) Romidine Clonidine Phentolamine Brimonidine Yohimbine Detomidine Idazoxan Lofexidine Atipamezole Xylazine Tizanidine Guanfacine Amitraz (Beta blockers) Dobutamine Isoprenaline Noradrenaline (Short/long) Gs: adenylate 2 cyclase Smooth muscle activated, Isoprenaline > epinephrine >> norepinephrine relaxation cAMP up (also Gi, see 2) Salbutamol (Albuterol in USA) Bitolterol mesylate Formoterol Isoprenaline Levalbuterol (Beta blockers) Butoxamine Propranolol Metoprolol Atenolol

2: A, B, C

Gi: adenylate cyclase inactivated, cAMP down

Isoprenaline > epinephrine = norepinephrine

Heart muscle contraction

Gs: adenylate cyclase activated, cAMP up

4 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

Metaproterenol Salmeterol Terbutaline Ritodrine Enhance lipolysis, promotes relaxation of detrusor muscle in the bladder

Gs: adenylate cyclase activated, cAMP up

Isoprenaline = norepinephrine > epinephrine

L-796568[2] Amibegron Solabegron

SR 59230A

There is no 1C receptor. At one time, there was a subtype known as C, but was found to be identical to one of the previously discovered

subtypes. To avoid confusion, naming was continued with the letter D.

receptors
receptors have several functions in common, but also individual effects. Common (or still unspecied) effects include: Vasoconstriction of arteries to heart (coronary artery).[3] Vasoconstriction of veins[4] Decrease motility of smooth muscle in gastrointestinal tract[5] 1 receptor Main article: Alpha-1 adrenergic receptor Alpha1-adrenergic receptors are members of the G protein-coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC). The PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2), which in turn causes an increase in inositol triphosphate (IP3) and diacylglycerol (DAG). The former interacts with calcium channels of endoplasmic and sarcoplasmic reticulum, thus changing the calcium content in a cell. This triggers all other effects. Specic actions of the 1 receptor mainly involve smooth muscle contraction. It causes vasoconstriction in many blood vessels, including those of
5 of 10 12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

the skin, gastrointestinal system, kidney (renal artery)[6] and brain.[7] Other areas of smooth muscle contraction are: ureter vas deferens hair (arrector pili muscles) uterus (when pregnant) urethral sphincter bronchioles (although minor to the relaxing effect of 2 receptor on bronchioles) blood vessels of ciliary body (stimulation causes mydriasis) Further effects include glycogenolysis and gluconeogenesis from adipose tissue[8] and liver, as well as secretion from sweat glands[8] and Na+ reabsorption from kidney.[8] Antagonists may be used in hypertension. 2 receptor Main article: Alpha-2 adrenergic receptor There are 3 highly homologous subtypes of 2 receptors: 2A, 2, and 2C. Specic actions of the 2 receptor include: inhibition of insulin release in the pancreas.[8] induction of glucagon release from the pancreas. contraction of sphincters of the gastrointestinal tract negative feedback in the neuronal synapses - presynaptic inhibition of noradrenalin release in CNS increased thrombocyte aggregation

receptors
1 receptor Main article: Beta-1 adrenergic receptor

6 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

Specic actions of the 1 receptor include: Increase cardiac output, by raising heart rate (positive chronotropic effect), increasing impulse conduction (positive dromotropic effect), and increasing contraction (positive inotropic effect), thus increasing the volume expelled with each beat (increased ejection fraction). Increase renin secretion from juxtaglomerular cell of kidney. Increase ghrelin secretion from the stomach[9] 2 receptor Main article: Beta-2 adrenergic receptor Specic actions of the 2 receptor include the following: Smooth muscle relaxation, e.g. in bronchi,[8] GI tract (decreased motility). Lipolysis in adipose tissue.[10] Anabolism in skeletal muscle.[11][12] Relax non-pregnant uterus Relax detrusor urinae muscle of bladder wall Dilate arteries to skeletal muscle Glycogenolysis and gluconeogenesis Stimulates insulin secretion Contract sphincters of GI tract Thickened secretions from salivary glands.[8] Inhibit histamine-release from mast cells Increase renin secretion from kidney Relaxation of Bronchioles (salbutamol, a beta 2 agonist relieves bronchiole constriction) Involved in brain - immune communication[13] 3 receptor Main article: Beta-3 adrenergic receptor Specic actions of the 3 receptor include:

7 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

Enhancement of lipolysis in adipose tissue. Beta-3 activating drugs could theoretically be used as weight-loss agents, but are limited by the side effect of tremors.

See also
Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

References
1. ^ Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG (November 2000). "G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels" (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez& artid=1301137) . Biophys. J. 79 (5): 254756. doi:10.1016/S0006-3495(00)76495-2 (http://dx.doi.org /10.1016%2FS0006-3495%2800%2976495-2) . PMC 1301137 (http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez& artid=1301137) . PMID 11053129 (http://www.ncbi.nlm.nih.gov/pubmed /11053129) . http://www.pubmedcentral.nih.gov /articlerender.fcgi?tool=pmcentrez&artid=1301137. 2. ^ Nisoli E, Tonello C, Landi M, Carruba MO (1996). "Functional studies of the rst selective 3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes" (http://molpharm.aspetjournals.org/cgi/content /abstract/49/1/7) . Mol. Pharmacol. 49 (1): 714. PMID 8569714 (http://www.ncbi.nlm.nih.gov/pubmed/8569714) . http://molpharm.aspetjournals.org/cgi/content/abstract/49/1/7. 3. ^ Woodman OL, Vatner SF (1987). "Coronary vasoconstriction mediated by 1- and 2-adrenoceptors in conscious dogs" (http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388) . Am. J. Physiol. 253 (2 Pt 2): H38893. PMID 2887122 (http://www.ncbi.nlm.nih.gov/pubmed/2887122) . http://ajpheart.physiology.org/cgi/content/abstract/253/2/H388. 4. ^ Elliott J (1997). "Alpha-adrenoceptors in equine digital veins: evidence for the presence of both 1- and 2-receptors mediating vasoconstriction". J. Vet. Pharmacol. Ther. 20 (4): 30817. doi:10.1046/j.1365-2885.1997.00078.x (http://dx.doi.org /10.1046%2Fj.1365-2885.1997.00078.x) . PMID 9280371 (http://www.ncbi.nlm.nih.gov/pubmed/9280371) . 5. ^ Sagrada A, Fargeas MJ, Bueno L (1987). "Involvement of 1 and 2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat" (http://www.pubmedcentral.nih.gov /articlerender.fcgi?tool=pmcentrez&artid=1433140) . Gut 28 (8): 9559. doi:10.1136/gut.28.8.955 (http://dx.doi.org/10.1136%2Fgut.28.8.955) . PMC 1433140 (http://www.pubmedcentral.gov /articlerender.fcgi?tool=pmcentrez&artid=1433140) . PMID 2889649 (http://www.ncbi.nlm.nih.gov/pubmed/2889649) . http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez& artid=1433140. 6. ^ Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA (1981). "Renal 1 and 2 adrenergic receptors: biochemical and pharmacological correlations" (http://jpet.aspetjournals.org/cgi/content /abstract/219/2/400) . J. Pharmacol. Exp. Ther. 219 (2): 4006. PMID 6270306 (http://www.ncbi.nlm.nih.gov/pubmed/6270306) . http://jpet.aspetjournals.org/cgi/content/abstract/219/2/400. ^ Circulation & Lung Physiology I (http://cim.ucdavis.edu/masters /sessions2002/session4_ica.doc) M.A.S.T.E.R. Learning Program, UC Davis School of Medicine ^ a b c d e f Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0. ^ Zhao, T. J.; Sakata, I.; Li, R. L.; Liang, G.; Richardson, J. A.; Brown, M. S. et al. (2010). "Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice". Proc Natl Acad Sci U S A 107 (36): 1586815873. doi:10.1073/pnas.1011116107 (http://dx.doi.org/10.1073%2Fpnas.1011116107) . PMID 20713709 (http://www.ncbi.nlm.nih.gov/pubmed/20713709) . ^ Large V, Hellstrm L, Reynisdottir S, et al. (December 1997). "Human

7.

8. 9.

10.

8 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function" (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez& artid=508512) . J. Clin. Invest. 100 (12): 300513. doi:10.1172/JCI119854 (http://dx.doi.org/10.1172%2FJCI119854) . PMC 508512 (http://www.pubmedcentral.gov /articlerender.fcgi?tool=pmcentrez&artid=508512) . PMID 9399946 (http://www.ncbi.nlm.nih.gov/pubmed/9399946) . http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez& artid=508512. 11. ^ Kline WO, Panaro FJ, Yang H, Bodine SC (February 2007). "Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol". J. Appl. Physiol. 102 (2): 7407.

doi:10.1152/japplphysiol.00873.2006 (http://dx.doi.org /10.1152%2Fjapplphysiol.00873.2006) . PMID 17068216 (http://www.ncbi.nlm.nih.gov/pubmed/17068216) . 12. ^ Kamalakkannan G, Petrilli CM, George I, et al. (April 2008). "Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure". J. Heart Lung Transplant. 27 (4): 45761. doi:10.1016/j.healun.2008.01.013 (http://dx.doi.org /10.1016%2Fj.healun.2008.01.013) . PMID 18374884 (http://www.ncbi.nlm.nih.gov/pubmed/18374884) . 13. ^ Elenkov, I. J., R. L. Wilder, et al. (2000). "The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system.". Pharmacol Rev 52 (4): 595638. PMID 11121511 (http://www.ncbi.nlm.nih.gov/pubmed/11121511) .

Further reading
Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Chapter 11: Noradrenergic transmission". Pharmacology (5th ed.). Elsevier Churchill Livingstone. ISBN 0-443-07145-4. Rang HP, Dale MM, Ritter JM, Flower RJ (2007). "Chapter 11: Noradrenergic transmission". Rang and Dale's Pharmacology (6th ed.). Elsevier Churchill Livingstone. pp. 169170. ISBN 0-443-06911-5.

External links
Alpha receptors illustrated (http://pharmacologycorner.com/alpha-receptors-1-2/) The Adrenergic Receptors (http://macromoleculeinsights.com/adrenergic.php) "Adrenoceptors" (http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1274) . IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org /GPCR/ChapterMenuForward?chapterID=1274. Basic Neurochemistry: - and -Adrenergic Receptors (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm.section.890) Brief overview of functions of the beta-3 receptor (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109691) Theory of receptor activation (http://cogprints.org/4095/) Desensitization of beta-1-receptors (http://cogprints.org/4093/) UMich Orientation of Proteins in Membranes protein/pdbid-2rh1 (http://opm.phar.umich.edu/protein.php?pdbid=2rh1) - 3D structure of beta-2 adrenergic receptor in membrane Retrieved from "http://en.wikipedia.org/w/index.php?title=Adrenergic_receptor&oldid=464960673" Categories: Adrenergic receptors G protein coupled receptors

9 of 10

12/10/11 10:15 PM

Adrenergic receptor - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Adrenergic_receptor

This page was last modied on 9 December 2011 at 15:16. Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms of use for details. Wikipedia is a registered trademark of the Wikimedia Foundation, Inc., a non-prot organization.

10 of 10

12/10/11 10:15 PM