Adrenergic receptor

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Adrenaline

Noradrenaline
The adrenergic receptors (or adrenoceptors) are a class of 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 response (e.g.
the fight-or-flight response). For instance, the heart rate will
increase and the pupils will dilate, energy will be mobilized, and
blood flow diverted from other non-essential organs to skeletal
muscle.
Contents
 [hide]

 1 Subtypes
o 1.1 Roles in
circulation
o 1.2 Comparison
o 1.3 α receptors
 1.3.1 α1 rece
ptor
 1.3.2 α2 rece
 ptor
o 1.4 β receptors
 1.4.1 β1 rece
ptor
 1.4.2 β2 rece
ptor
 1.4.3 β3 rece
ptor
 2 See also
 3 References
 4 Further reading
 5 External links
[edit]Subtypes
There are two main groups of adrenergic receptors, α and β, with
several subtypes.

 α receptors have the subtypes α1 (a Gq coupled receptor)

and α2 (a Gi coupled receptor). Phenylephrine is a selective
agonist of the α receptor.
 β receptors have the subtypes β1, β2 and β3. All three are
linked to Gs proteins (although β2 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.
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 (more
details...)
The mechanism of adrenergic receptors. Adrenaline or
noradrenaline are receptor ligands to either α1, α2 or β-adrenergic
receptors. α1 couples to Gq, which results in increased
intracellular Ca2+ which results in smooth muscle contraction. α2, on
the other hand, couples to Gi, which causes a decrease
of cAMP activity, resulting in e.g. smooth muscle relaxation. β
receptors couple to Gs, and increases intracellular cAMP activity,
resulting in e.g. heart muscle contraction, smooth muscle
relaxation andglycogenolysis.
[edit]Roles in circulation
Adrenaline reacts with both α- and β-adrenoreceptors, causing
vasoconstriction and vasodilation, respectively. Although α
receptors are less sensitive to epinephrine, when activated, they
override the vasodilation mediated by β-adrenoreceptors. The
result is that high levels of circulating epinephrine cause
vasoconstriction. At lower levels of circulating epinephrine, β-
adrenoreceptor stimulation dominates, producing an overall
vasodilation.
[edit]Comparison
Selected
Recep
Agonist potency order action Mechanism Agonists Antagonists
tor
of agonist

:
α1 Norepinephrine >epinephrine  Smooth Gq: phospholipase (Alpha-1
A, B,  >> isoprenaline muscle contr C (PLC) (Alpha-1 agonists) blockers)
D† action activated, IP3 and calc
ium up
 Noradren  Alfuzo
aline sin
 Phenylep  Doxaz
hrine osin
 Methoxa  Pheno
mine xybenzami
 Cirazoline ne

 Xylometa  Phento
zoline lamine
 Prazos
 in
 Tamsu
losin
 Terazo
sin

(TCA:s)

 Amitri
ptyline
 Clomi
pramine
 Doxep
in
 Trimip
ramine

:
α2 Epinephrine ≥norepinephrine  Smooth Gi: adenylate (Alpha-2
A, B,  >>isoprenaline muscle const cyclase inactivated,c (Alpha-2 agonists) blockers)
C riction and AMP down
neurotransmi
tter  Dexmedet  Phento
inhibition omidine lamine
 Medetomi  Yohim
dine bine
 Romifidin  Idazox
e an
 Clonidine  Atipa
 Brimonidi mezole
ne
 Detomidi
ne
 Lofexidin
e
 Xylazine
 Tizanidin
e
  Guanfacin
e
 Amitraz

 Noradren (Beta blockers)

aline
Heart Gs: adenylate  Metop
Isoprenaline > epinephrine =n  Isoprenali
β1 muscle contr cyclase activated,cA
orepinephrine rolol
action MP up ne
 Atenol
 Dobutami
ol
ne

(Short/long)

 Salbutam
ol(Albuterol i
n USA)
 Bitolterol
mesylate
 Formoter
(Beta blockers)
ol
Gs: adenylate
Smooth  Isoprenali  Butoxa
Isoprenaline > epinephrine>>  cyclase activated,cA
β2 muscle relax
norepinephrine MP up (also Gi, ne mine
ation
see β2)
 Levalbute  Propra
rol nolol
 Metaprote
renol
 Salmetero
l
 Terbutalin
e
 Ritodrine

β3 Isoprenaline =norepinephrine  Enhance lipo Gs: adenylate

 L-796568   SR
> epinephrine lysis cyclase activated,cA
MP up [2]
59230A
 Amibegro
n
  Solabegro
n

†
There is no α1C 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.
[edit]α receptors
α receptors have several functions in common, but also individual
effects. Common (or still unspecified) effects include:

 Vasoconstriction of arteries to heart (coronary artery).[3]
 Vasoconstriction of veins[4]
 Decrease motility of smooth muscle in gastrointestinal tract[5]
[edit]α1 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.
Specific actions of the α1 receptor mainly involve smooth muscle
contraction. It causes vasoconstriction in many blood
vessels including those of 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
β2 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.
[edit]α2 receptor
Main article: Alpha-2 adrenergic receptor
There are 3 highly homologous subtypes of
α2 receptors: α2A, α2Β, and α2C.
Specific actions of the α2 receptor include:

 inhibition of insulin release in pancreas.[8]

 induction of glucagon release from pancreas.
 contraction of sphincters of the gastrointestinal tract
 negative feedback in the neuronal synapses
[edit]β receptors
[edit]β1 receptor
Main article: Beta-1 adrenergic receptor
Specific actions of the β1 receptor include:

 Increase cardiac output, by raising heart rate (positive

chronotropic effect) and increasing impulse conduction and
increasing contraction 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]
[edit]β2 receptor
Main article: Beta-2 adrenergic receptor
Specific actions of the β2 receptor include the following:

 Smooth muscle relaxation, e.g. in bronchi.[8]

 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
 Contract sphincters of GI tract
 Thickened secretions from salivary glands.[8]
 Inhibit histamine-release from mast cells
 Increase renin secretion from kidney
[edit]β3 receptor
Main article: Beta-3 adrenergic receptor
Specific actions of the β3 receptor include:

 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.