The 

adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are

targets of many catecholamines like norepinephrine (noradrenaline)
and epinephrine (adrenaline) produced by the body, but also many medications like beta
blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood
pressure and asthma, for example.
Many 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 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[edit]
Main article: History of catecholamine research

Epinephrine

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:

1. There were (at least) two different types of neurotransmitters released from
sympathetic nerve terminals, or
2. 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,[1] 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 ergotoxine, the blood pressure decreased.[2][3] 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,
[4]
 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.[5] 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,[6] 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[edit]

The mechanism of adrenoreceptors. Adrenaline or noradrenaline are receptor ligands to either α1, α2 or β-

adrenoreceptors. The α1 couples to Gq, which results in increased intracellular Ca2+ and subsequent smooth
muscle contraction. The α2, on the other hand, couples to Gi, which causes a decrease in neurotransmitter
release, as well as a decrease of cAMP activity resulting in smooth muscle contraction. The β receptor
couples to Gs and increases intracellular 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 α1, α2 or β-adrenoreceptors. The α1 couples to Gq, which results in increased
intracellular Ca2+ and subsequent smooth muscle contraction. The α2, on the other hand, couples
to Gi, which causes a decrease in neurotransmitter release, as well as a decrease
of cAMP activity resulting in smooth muscle contraction. The β receptor couples to Gs and
increases intracellular 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 are divided to α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor)[7]

o α1 has 3 subtypes: α1A, α1B and α1D[a]
o α2 has 3 subtypes: α2A, α2B and α2C
 β are divided to β1, β2 and β3. All 3 are coupled to Gs proteins, but β2 and β3 also
couple to Gi[7]
Gi and Gs are linked to adenylyl cyclase. Agonist binding thus causes a rise in the intracellular
concentration of the second messenger (Gi inhibits the production of cAMP) cAMP. Downstream
effectors of cAMP include cAMP-dependent protein kinase (PKA), which mediates some of the
intracellular events following hormone binding.

Roles in circulation[edit]
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 α1 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 β2 response is greater than that of α1, 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 β2 adrenoreceptor than the α1 adrenoreceptor, producing vasodilation followed by
decrease of peripheral vascular resistance.[8]

Subtypes[edit]
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.

Rec
Agonist potency Antagonist
ept Agonist action Mechanism Agonists
order s
or

(Alpha-1
(Alpha-1
α1:  Norepinephrine >  Smooth Gq: phospho blockers)
agonists)
A, B epinephrine >> is muscle contraction,  lipase
, D[a] oprenaline[9] mydriasis, vasoconst C (PLC)  A
riction in the skin, activated, IP  No
c
mucosa and 3, and DAG,
rad
e
abdominal viscera & rise ren
p
sphincter contraction in calcium[7] ali
r
of the GI ne
o
tract and urinary  Ph m
bladder en a
yle z
phr i
ine n
 Me e
tho  A
xa lf
mi u
 ne z
 Cir o
az s
oli i
ne n
 Xyl  D
om o
eta x
zoli a
ne z
 Mi o
do s
dri i
ne n
 Me  P
tar h
am e
ino n
l o
 Chl x
oro y
eth b
ylcl e
oni n
din z
e a
m
 Ad
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ren
n
os
e
wit
ch  P
es h
(ph e
oto n
swi t
tch o
abl l
e a a
go m
nis i
ts) n
[10] e
 P
r
a
z
o
s
i
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 T
a
m
s
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l
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s
i
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 T
e
r
a
z
o
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 T
r
a
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o
d
o
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(TCAs)

 C
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m
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 D
o
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e
p
i
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 T
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  T
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a
t
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p
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a
l
a
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ti
p
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y
c
h
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ti
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s
Antihistamin
es (H1
antagonists)

 H
y
d
r
o
x
y
z
i
n
e
α2:  Epinephrine = no Smooth Gi: adenylat (Alpha-2
(Alpha-2
A, B repinephrine >> i muscle mixed e blockers)
agonists)
, C soprenaline[9] effects, cyclase inac
norepinephrine tivated, cAM  P
(noradrenaline) P down[7]  Ag
h
inhibition, platelet ac ma
e
tivation tin
n
e
o
 De x
xm
 ed
eto y
mi b
din e
e n
 Me z
det a
om m
idi i
ne n
 Ro e
mif  P
idi h
ne e
 Clo n
nid t
ine o
 Chl l
oro a
eth m
ylcl i
oni n
din e
e  Y
 Bri o
mo h
nid i
ine m
 De b
to i
mi n
din e
e  I
 Lof d
exi a
din z
e o
 Xyl x
azi a
ne n
 Tiz  A
ani ti
din p
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m
 Gu
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anf
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aci
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 Am e
itra
 T
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 T
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a
t
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p
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a
n
ti
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c
h
o
ti
c
s
β1 Isoprenaline > no Positive chronotropic Gs: adenylat (β1-adrenergic (Beta
repinephrine > ep , dromotropic and in e agonist) blockers)
inephrine[9] otropic effects, cyclase acti
increased amylase s vated, cAM  Do  M
ecretion P up[7] but e
am t
ine o
 Iso p
pre r
nal o
ine l
 No o
rad l
ren  A
ali t
ne e
n
o
l
o
l
  B
i
s
o
p
r
o
l
o
l
 P
r
o
p
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a
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o
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o
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 T
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 N
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b
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o
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 V
o
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ti
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x
e
ti
n
e
β2 Isoprenaline > ep Smooth Gs: adenylat (β2-adrenergic (Beta
inephrine > norep muscle relaxation e agonist) blockers)
inephrine[9] (bronchodilation for cyclase acti
example) vated, cAM  Sal  B
P up but u
(also Gi, am t
see α2)[7] ol ( o
Alb x
 a
m
ute i
rol n
in e
US
 T
A)
i
 Bit m
olt o
ero l
l o
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syl
 P
ate
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 For o
mo p
ter r
ol a
 Iso n
pre o
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ine o
 Le l
val  I
but C
ero I
l -
 Me 1
tap 1
rot 8
ere ,
nol 5
 Sal 5
me 1
ter  P
ol a
 Ter r
but o
ali x
ne e
 Rit ti
odr n
ine e
[1
1]

β3 Isoprenaline > no Enhance lipolysis, Gs: adenylat (β3-adrenergic (Beta

repinephrine = ep promotes relaxation e agonist) blockers)
inephrine[9] of detrusor muscle in cyclase acti
the bladder vated, cAM  L-  S
P up 79 R
(also Gi, 65
see α2)[7] 68[1 5
2]
9
 Am 2
ibe 3
 gro
n
 Sol
ab
egr
on 0
A
 Mir
ab
egr
on

α receptors[edit]
α receptors have actions in common, but also individual effects. Common (or still receptor
unspecified) actions include:

 vasoconstriction[13]
 decreased flow of smooth muscle in gastrointestinal tract[14]
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).[7]
α1 receptor[edit]
Main article: Alpha-1 adrenergic receptor
α1-adrenoreceptors are members of the Gq 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, including a prominent slow after depolarizing current (sADP) in
neurons.[15]
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)
[16]
 and brain.[17] Other areas of smooth muscle contraction are: