From Wikipedia, the free encyclopedia

Epinephrine

Norepinephrine

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 β₂-adrenergic receptors.)

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 G_q, which results in incerased intracellular Ca²⁺ which results in e.g. smooth muscle contraction. α₂, on the other hand, couples to G_i, which causes a decrease of cAMP activity, resulting in e.g. smooth muscle contraction. β receptors couple to G_s, 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.

• α receptors bind norepinephrine and epinephrine, though norepinephrine has higher affinity. Phenylephrine is a selective agonist of the α receptor. They exist as α₁-adrenergic receptors and α₂-adrenergic receptors.
• β receptors are linked to G_s proteins, which in turn are linked to adenylyl 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.

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 have several functions in common, but also individual effects. Common (or still unspecified) effects include:

• Vasoconstriction of arteries to heart (coronary artery).^[2]
• Vasoconstriction of veins^[3]
• Decrease motility of smooth muscle in gastrointestinal tract^[4]

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), which causes an increase in IP3 and calcium. This triggers all other effects.

Specific actions of the α₁ receptor mainly involves smooth muscle contraction. It causes vasoconstriction in blood vessels of skin & gastrointestinal system and to kidney (renal artery)^[5] and brain.^[6]. Other areas of smooth muscle contraction are for instance:

• ureter
• hairs (arrector pili muscles)
• uterus (when pregnant)
• urethral sphincter
• bronchioles (although minor to the relaxing effect of β₂ receptor on bronchioles)

Further effects include glycogenolysis and gluconeogenesis from adipose tissue^[7] and liver, as well as secretion from sweat glands^[7] and Na⁺ reabsorption from kidney.^[7]

Antagonists may be used in hypertension.

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.^[7]
• induction of glucagon release from pancreas.
• contraction of sphincters of the gastrointestinal tract

Main article: Beta-1 adrenergic receptor

Specific actions of the β₁ receptor include:

• Increase cardiac output
• Renin release from juxtaglomerular cells.^[7]
• Lipolysis in adipose tissue.^[7]

Main article: Beta-2 adrenergic receptor

The 3D crystallographic structure of the β₂-adrenergic receptor has been determined (PDB 2R4R, 2R4S, 2RH1).^[8][9][10]

Specific actions of the β₂ receptor include:

• Smooth muscle relaxation, e.g. in bronchi.^[7]
• Relax urinary sphincter.
• 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.^[7]
• Inhibit histamine-release from mast cells
• Increase renin secretion from kidney

Main article: Beta-3 adrenergic receptor

Specific actions of the β₃ receptor include:

• Enhancement of lipolysis in adipose tissue.

• Beta adrenergic receptor kinase
• Beta adrenergic receptor kinase-2

• 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, 169-170. ISBN 0-443-06911-5. 

• The Adrenergic Receptors
• IUPHAR GPCR Database - Adrenoceptors
• Basic Neurochemistry: α- and β-Adrenergic Receptors
• Brief overview of functions of the beta-3 receptor
• Theory of receptor activation
• Desensitization of beta-1-receptors
• UMich Orientation of Proteins in Membranes protein/pdbid-2rh1 - 3D structure of beta-2 adrenergic receptor in membrane

This membrane protein-related article is a stub. You can help Wikipedia by expanding it.