Adrenergic receptor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines adrenaline and noradrenaline (called epinephrine and norepinephrine in the United States), and are activated by these.

Many cells possess these receptors, and the binding of an agonist will generally cause a sympathetic response (ie 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 organs to skeletal muscle.(Note: Sympathetic activity will result in vasodilation of coronary arteries via the beta-2 adrenergic receptors.)

Subtypes

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 incerased intracellular Ca2+ which results in e.g. smooth muscle contraction. α2, on the other hand, couples to Gi, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction. β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

There are several types of adrenergic receptors, but there are two main groups: α-Adrenergic and β-Adrenergic.

Comparison

Receptor type Agonist potency order Selected action
of agonist
Mechanism Agonists Antagonists
α1:
ADRA1A, ADRA1B, ADRA1D
noradrenaline≥ adrenaline >> isoprenaline smooth muscle contraction Gq: phospholipase C (PLC) activated, IP3 and calcium up noradrenaline
phenylephrine
methoxamine
Cirazoline
(Alpha blockers)
phenoxybenzamine
phentolamine
prazosin
tamsulosin
terazosin
α2:
ADRA2A, ADRA2B, ADRA2C
adrenaline > noradrenaline >> isoprenaline smooth muscle contraction Gi: adenylate cyclase inactivated, cAMP down clonidine
lofexidine
xylazine
Tizanidine
Guanfacine
(Alpha blockers)
yohimbine
β1:
ADRB1
isoprenaline > noradrenaline > adrenaline heart muscle contraction Gs: adenylate cyclase activated, cAMP up noradrenaline
isoprenaline
dobutamine
(Beta blockers)
metoprolol
atenolol
β2:
ADRB2
isoprenaline > adrenaline > noradrenaline smooth muscle relaxation Gs: adenylate cyclase activated, cAMP up (Short/long)
salbutamol (albuterol in USA)
bitolterol mesylate
formoterol
isoproterenol
levalbuterol
metaproterenol
salmeterol
terbutaline
(Beta blockers)
butoxamine
propranolol
ritodrine
β3:
ADRB3
isoprenaline > noradrenaline = adrenaline Enhance lipolysis Gs: adenylate cyclase activated, cAMP up L-796568
CL 316,243
LY 368842
Ro 40-2148
(Beta blockers)
SR 59230A

The absence of "ADRA1C" is intentional. At one time, there was a subtype known as C, but was found to be one of the previously discovered subtypes. To avoid confusion, it was decided that there would never be a C subtype again and so if any new subtypes were discovered, naming would start with D.

α receptors

α receptors have several functions in common, but also individual effects. Common effects include:

α1 receptor

Specific actions of the α1 receptor include:

α2 receptor

Specific actions of the α2 receptor include:

β receptors

As with α receptors, there are common actions of all β receptors, in addition to specific actions of each subtype. Common actions include:

β1 receptor

Specific actions of the β1 receptor include:

β2 receptor

Specific actions of the β2 receptor include:

Muscular system

Circulatory system

digestive system

Other

The 3D structure of β2-Adrenergic receptor has been determined [2].

β3 receptor

Specific actions of the β3 receptor include: Enhance lipolysis in adipose tissue.

Diagrams

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...)

See also

References

  • Rang HP, Dale MM, Ritter JM, Moore PK (2003). "Ch. 11". Pharmacology. Elsevier Churchill Livingstone. ISBN 0-443-07145-4.
  • Rang HP, Dale MM, Ritter JM, Flower RJ (2007). "Ch. 11". Rang and Dale's Pharmacology. Elsevier Churchill Livingstone. pp. 169–170. ISBN 0-443-06911-5.
  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 Neuroscience (Purves), Third Edition, table 20:2
  2. Excitatory alpha1-adrenergic receptors predominate over inhibitory beta-receptors in rabbit dorsal detrusor: "alpha1-AR subtypes responsible for norepinephrine induced contraction of rabbit dorsal detrusor smooth muscle". Chou EC, Capello SA, Levin RM, Longhurst PA.
  3. Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists EE Wright and ER Simpson
  4. Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia. Trovik TS, Vaartun A, Jorde R, Sager G.. Eur J Clin Pharmacol. 1995;48(5):327-32. PMID: 8641318

External links


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