Adrenergic receptor

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
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 Gs 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.

Comparison
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:
 * Vasoconstriction of arteries to kidney (renal artery), heart (coronary artery), viscera, brain, erectile tissue and salivary glands.
 * Vasoconstriction of veins
 * Decrease motility of smooth muscle in gastrointestinal tract
 * Contractions in male genitalia during ejaculation

α1 receptor
Specific actions of the α1 receptor include:
 * Vasoconstriction in blood vessels of skin & gastrointestinal system


 * Smooth muscle contraction in:
 * ureter
 * hairs (arrector pili muscles)
 * uterus (when pregnant)
 * urethral sphincter
 * ureters
 * bronchioles (although minor to the relaxing effect of β2 receptor on bronchioles)


 * urinary bladder contraction


 * Smooth muscle relaxation in:
 * iris


 * Positive ionotropic effect on heart muscle.


 * Secretion from salivary gland.


 * Increase salivary potassium levels.


 * Glycogenolysis and gluconeogenesis from adipose tissue and liver.


 * Secretion from sweat glands.


 * Na+ reabsorption from kidney.

α2 receptor
Specific actions of the α2 receptor include:


 * Mediates synaptic transmission in pre- and postsynaptic nerve terminals.


 * Inhibition of lipolysis in adipose tissue.


 * inhibition of insulin release in pancreas.
 * induction of glucagon from pancreas.


 * Aggregation of platelets


 * contraction of sphincters of the gastrointestinal tract

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:


 * Stimulation of viscous, amylase-filldes secretions from salivary glands.

β1 receptor
Specific actions of the β1 receptor include:
 * Increase cardiac output
 * Increase heart rate in sinoatrial node (SA node) (chronotropic effect)
 * Increase atrial cardiac muscle contractility. (inotropic effect)
 * Increases contractility and automaticity of ventricular cardiac muscle.
 * Increases conduction and automaticity of atrioventricular node (AV node)


 * Renin release from juxtaglomerular cells.


 * Lipolysis in adipose tissue.


 * Receptor also present in cerebral cortex.

β2 receptor
Specific actions of the β2 receptor include:

Muscular system
 * Smooth muscle relaxation in uterus (when non-pregnant), GI tract , blood vessels and bronchi (agonists can be useful in treating asthma)
 * Relax urinary sphincter.
 * Relax detrusor urinae muscle‎ of bladder wall

Circulatory system
 * Increase cardiac output (minor degree compared to β1.
 * Increase heart rate in sinoatrial node (SA node) (chronotropic effect)
 * Increase atrial cardiac muscle contractility. (inotropic effect)
 * Increases contractility and automaticity of ventricular cardiac muscle.


 * Dilate hepatic artery


 * Dilate arteries to skeletal muscle

digestive system
 * Glycogenolysis and gluconeogenesis in liver.


 * Glycogenolysis and lactate release in skeletal muscle.


 * Contract sphincters of GI tract


 * Insulin secretion from pancreas


 * Thickened secretions from salivary glands.

Other


 * Inhibit histamine-release from mast cells


 * Increase protein content of secretions from lacrimal glands


 * Increase renin secretion from kidney


 * Receptor also present in cerebellum.

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

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