Adrenergic receptor

The adrenergic receptors (or adrenoceptors) are a class of metabotropic 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 (or sympathomimetic) 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.

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), 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.



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.

Comparison
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 cardiac muscle. Increased cAMP will promote relaxation in smooth muscle, while promoting increased contractility and pulse rate in cardiac muscle.

†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.

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).
 * Vasoconstriction of veins
 * Decrease motility of smooth muscle in gastrointestinal tract

α1 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) and brain. 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 and liver, as well as secretion from sweat glands and Na+ reabsorption from kidney.

Antagonists may be used in hypertension.

α2 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 the pancreas.
 * induction of glucagon release from the pancreas.
 * contraction of sphincters of the gastrointestinal tract
 * negative feedback in the neuronal synapses - presynaptic inhibition of noradrenalin release in CNS
 * increased thrombocyte aggregation

β1 receptor
Specific actions of the β1 receptor include:
 * Increase cardiac output, by raising heart rate (positive chronotropic effect), 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

β2 receptor
Specific actions of the β2 receptor include the following:
 * Smooth muscle relaxation, e.g. in bronchi, GI tract (decreased motility).
 * Lipolysis in adipose tissue.
 * Anabolism in skeletal muscle.
 * Relax non-pregnant uterus
 * Relax detrusor urinae muscle‎ of bladder wall
 * Dilate arteries to skeletal muscle
 * Glycogenolysis and gluconeogenesis
 * Stimulates insulin secretion
 * Contract sphincters of GI tract
 * Thickened secretions from salivary glands.
 * Inhibit histamine-release from mast cells
 * Increase renin secretion from kidney
 * Relaxation of Bronchioles (salbutamol, a beta 2 agonist relieves bronchiole constriction)
 * Involved in brain - immune communication

β3 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.