Adrenergic receptor

receptors have the subtypes 1 (a G coupled receptor) and 2 (a G coupled receptor[2] ).

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

Epinephrine

Norepinephrine
The adrenergic receptors (or adrenoceptors) are a
class of G protein-coupled receptors that are targets
of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).
Many cells possess these receptors, and the binding of
a catecholamine to the receptor will generally stimulate
the sympathetic nervous system. The sympathetic nervous system is responsible for the ght-or-ight response,
which includes widening the pupils of the eye, mobilizing energy, and diverting blood ow from non-essential
organs to skeletal muscle.

History

Raymond Ahlquist, Professor of Pharmacology at Medical College of Georgia, published a paper concerning
adrenergic nervous transmission in 1948[1] but its signicance was largely ignored at that time. However, in
1954 he was able to incorporate his ndings in a textbook,
Drills Pharmacology in Medicine, and thereby rmly establish the essential role played by and receptor sites
in the adrenaline/nor-adrenaline cellular mechanism. His
discovery would revolutionise advances in pharmacotherapeutic research, allowing the selective design of specic molecules to target medical ailments rather than rely
upon traditional research into the ecacy of pre-existing
herbal medicines.

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+ and subsequent smooth muscle contraction. 2 , on the
other hand, couples to Gi, which causes a decrease in neurotransmitter release, as well as a decrease of cAMP activity and a resulting and smooth muscle contraction. receptors couple to Gs,
and increases intracellular cAMP activity, resulting in e.g. heart
muscle contraction, smooth muscle relaxation and glycogenolysis.

Categories

2.1 Roles in circulation

There are two main groups of adrenergic receptors, and Epinephrine (adrenaline) reacts with both - and , with several subtypes.
adrenoreceptors, causing vasoconstriction and vasodila1

2 CATEGORIES

tion, respectively. Although receptors are less sensitive to epinephrine, when activated, they override the vasodilation mediated by -adrenoreceptors because there
are more peripheral 1 receptors than -adrenoreceptors.
The result is that high levels of circulating epinephrine
cause vasoconstriction. At lower levels of circulating
epinephrine, -adrenoreceptor stimulation dominates,
producing vasodilation followed by decrease of peripheral vascular resistance.

2.2

ureter
vas deferens
hair (arrector pili muscles)
uterus (when pregnant)
urethral sphincter
urothelium and lamina propria[10]
bronchioles (although minor due to the relaxing effect of 2 receptor on bronchioles)

Subtypes

Smooth muscle behavior is variable depending on

anatomical location.
Smooth muscle contraction/relaxation is generalized below. One important
note is the dierential eects 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.
[5]

blood vessels of ciliary body (stimulation causes

mydriasis)
Further
eects
include
glycogenolysis
and
gluconeogenesis from adipose tissue[11] and liver,
as well as secretion from sweat glands[11] and Na+
reabsorption from kidney.[11]
Antagonists may be used primarily in hypertension,
anxiety disorder, and panic attacks.

There is no C receptor. At one time, there was a sub- 2.3.2 receptor

2
type known as C, but was found to be identical to one of
the previously discovered subtypes. To avoid confusion, Main article: Alpha-2 adrenergic receptor
naming was continued with the letter D.

The 2 receptor couples to the G/ protein.[2] It is a presynaptic receptor, causing negative feedback on, for ex2.3 receptors
ample, norepinephrine. When NA is released into the
receptors have several functions in common, but also synapse, it feeds back on the 2 receptor, causing less
individual eects. Common (or still unspecied) eects NA release from the presynaptic neuron. This decreases
the eect of NA. There are also 2 receptors on the nerve
include:
terminal membrane of the post-synaptic adrenergic neuron.
Vasoconstriction of veins[6]
Decrease motility of
gastrointestinal tract[7]

smooth

muscle

in There are 3 highly homologous subtypes of 2 receptors:

A, , and C.
Specic actions of the 2 receptor include:

2.3.1

1 receptor

inhibition of insulin release in the pancreas.[11]

Main article: Alpha-1 adrenergic receptor

induction of glucagon release from the pancreas.

contraction of sphincters of the gastrointestinal tract

1 -adrenergic receptors are members of the G protein negative feedback in the neuronal synapses - presycoupled receptor superfamily.
Upon activation, a
naptic inhibition of noradrenalin (NA) release in
heterotrimeric G protein, G , activates phospholipase
CNS
C (PLC). The PLC cleaves phosphatidylinositol 4,5bisphosphate (PIP2), which in turn causes an increase
increased thrombocyte aggregation
in inositol triphosphate (IP3) and diacylglycerol (DAG).
The former interacts with calcium channels of endoplasmic and sarcoplasmic reticulum, thus changing the cal- 2.4 receptors
cium content in a cell. This triggers all other eects.
Specic actions of the receptor mainly involve smooth 2.4.1 1 receptor
1

muscle contraction. It causes vasoconstriction in many

blood vessels, including those of the skin, gastrointestinal Main article: Beta-1 adrenergic receptor
system, kidney (renal artery)[8] and brain.[9] Other areas
of smooth muscle contraction are:
Specic actions of the 1 receptor include:

3
Increase cardiac output by increasing heart rate
(positive chronotropic eect), conduction velocity
(positive dromotropic eect), and stroke volume (by
enhancing contractilitypositive inotropic eect).

Increase renin secretion from kidney

Increase renin secretion from juxtaglomerular cells

of the kidney.

Involved in brain - immune communication[16]

Increase ghrelin secretion from the stomach.[12]

Relaxation of Bronchioles (salbutamol, a 2 agonist

relieves bronchiole constriction)

2.4.3 3 receptor
Main article: Beta-3 adrenergic receptor

2.4.2

2 receptor

Main article: Beta-2 adrenergic receptor

Specic actions of the 2 receptor include the following:

Specic actions of the 3 receptor include:

Enhancement of lipolysis in adipose tissue. 3 activating drugs could theoretically be used as weightloss agents, but are limited by the side eect of
tremors.

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

4 References
[1] Ahlquist R.P. A Study of the Adenotrophic Receptors,
Am. J. Physiol. 1948 153:586-600

Beta-2 adrenergic receptor (PDB 2rh1), which stimulates cells

to increase energy production and utilization. The membrane is
shown schematically with a gray stripe.

Smooth muscle relaxation, e.g. in bronchi,[11] GI

tract (decreased motility).
Lipolysis in adipose tissue.[13]
Anabolism in skeletal muscle.

[14][15]

Relax non-pregnant uterus

Relax detrusor urinae muscle of bladder wall
Dilate arteries to skeletal muscle
Glycogenolysis and gluconeogenesis
Inhibits insulin secretion
Contract sphincters of GI tract
Thickened secretions from salivary glands.[11]
Inhibit histamine-release from mast cells

[2] Kou Qin, Pooja R. Sethi and Nevin A. Lambert (August

2008). Abundance and stability of complexes containing
inactive G protein-coupled receptors and G proteins. The
FASEB Journal 22 (8): 29202927. doi:10.1096/fj.08105775. PMC 2493464. PMID 18434433.
[3] 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. Biophys. J. 79 (5): 2547
56. Bibcode:2000BpJ....79.2547C. doi:10.1016/S00063495(00)76495-2. PMC 1301137. PMID 11053129.
[4] 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.
Mol. Pharmacol. 49 (1): 714. PMID 8569714.
[5] english
[6] 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.13652885.1997.00078.x. PMID 9280371.
[7] Sagrada A, Fargeas MJ, Bueno L (1987). Involvement
of 1 and 2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat. Gut 28 (8): 955
9. doi:10.1136/gut.28.8.955. PMC 1433140. PMID
2889649.

[8] Schmitz JM, Graham RM, Sagalowsky A, Pettinger WA

(1981). Renal 1 and 2 adrenergic receptors: biochemical and pharmacological correlations. J. Pharmacol. Exp. Ther. 219 (2): 4006. PMID 6270306.
[9] Circulation & Lung Physiology I M.A.S.T.E.R. Learning
Program, UC Davis School of Medicine
[10] Moro, C; Tajouri, L; Chess-Williams, R (January 2013).
Adrenoceptor function and expression in bladder urothelium and lamina propria. Urology. 81 (1): 211.e17.
doi:10.1016/j.urology.2012.09.011. PMID 23200975.

EXTERNAL LINKS

6 External links
Alpha receptors illustrated
The Adrenergic Receptors
Adrenoceptors. IUPHAR Database of Receptors
and Ion Channels. International Union of Basic and
Clinical Pharmacology.
Basic Neurochemistry: - and -Adrenergic Receptors

[11] Fitzpatrick, David; Purves, Dale; Augustine, George

(2004). Table 20:2. Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.

Brief overview of functions of the 3 receptor

[12] 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
Proc Natl Acad Sci U S A 107 (36):
mice.
1586815873.
Bibcode:2010PNAS..10715868Z.
doi:10.1073/pnas.1011116107. PMC 2936616. PMID
20713709.

Desensitization of 1 receptors

[13] Large V, Hellstrm L, Reynisdottir S et al. (December

1997). Human beta-2 adrenoceptor gene polymorphisms
are highly frequent in obesity and associate with altered
adipocyte beta-2 adrenoceptor function. J. Clin. Invest. 100 (12): 300513. doi:10.1172/JCI119854. PMC
508512. PMID 9399946.
[14] Kline WO, Panaro FJ, Yang H, Bodine SC (February
2007). Rapamycin inhibits the growth and musclesparing eects of clenbuterol. J. Appl. Physiol. 102 (2):
7407. doi:10.1152/japplphysiol.00873.2006. PMID
17068216.
[15] 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. PMID 18374884.
[16] 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.

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 Dales Pharmacology (6th ed.).
Elsevier
Churchill Livingstone. pp. 169170. ISBN 0-44306911-5.

Theory of receptor activation

UMich Orientation of Proteins in Membranes

protein/pdbid-2rh1 - 3D structure of 2 adrenergic
receptor in membrane

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7.3

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