Alpha-1 adrenergic receptor

The alpha-1 adrenergic receptor (α1-AR) is an adrenergic receptor with the primary effect of vasoconstriction.

Effect
The α1 receptor has several, general, functions in common with other α-receptors, but also has specific effects.

General
Common (or still unspecified) effects include:
 * Vasoconstriction of arteries to heart (coronary artery).
 * Vasoconstriction of veins
 * Decrease motility of smooth muscle in gastrointestinal tract

Specific
The primary effect is on smooth muscle, which mainly constrict. However, there are other functions as well.

Smooth muscle
In smooth muscle of blood vessels the principal effect is vasoconstriction. Blood vessels with α1 receptors are present in the skin, the sphincters of gastrointestinal system, kidney (renal artery) and brain. During the fight-or-flight response vasoconstriction results in the decreased blood flow to these organs. This accounts for an individual's skin appearing pale when frightened.

It also induces contraction of the urinary bladder, although this effect is minor compared to the relaxing effect of β-2 adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to delay micturition during stress.

Other effects are on smooth muscle are contraction in:
 * ureter
 * hairs (arrector pili muscles)
 * uterus (when pregnant)
 * urethral sphincter
 * bronchioles (although minor to the relaxing effect of β2 receptor on bronchioles)
 * iris dilator muscle
 * seminal tract, resulting in ejaculation

In a few areas the result on smooth muscle is relaxation. These include:
 * The rest of the GI tract than the sphincters.
 * Blood vessels of erectile tissue.

Other

 * Positive ionotropic effect on heart muscle. (α1<<β1).


 * &uarr;Secretion from salivary gland.


 * Increase salivary potassium levels.


 * Glycogenolysis and gluconeogenesis from adipose tissue and liver.


 * Secretion from sweat glands.


 * Na+ reabsorption from kidney.
 * Stimulate proximal tubule NHE3
 * Stimulate proximal tubule basolateral Na-K ATPase


 * Activate mitogenic responses and regulate growth and proliferation of many cells.

Activity During Exercise
During exercise these alpha-1 receptors can be selectively blocked by sympathetic nervous activity, allowing the beta-2 receptors (which mediate vasodilation) to dominate. Note that only the alpha-1 receptors in exercising muscle will be blocked. Resting muscle will not have its alpha-1 receptors blocked, and hence the overall effect there will be alpha-1 mediated vasocontriction.

Mechanism
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.

Agonists
Agonists include:
 * noradrenaline
 * adrenaline
 * isoprenaline
 * phenylephrine* (decongestant)
 * methoxamine*
 * cirazoline*

* denotes selective agonists to the receptor.

Noradrenaline has higher receptor affinity than has adrenaline, which, in turn has much higher affinity than isoprenaline.

Antagonsts
Antagonists are various ''alpha blockers:
 * mirtazapine (NaSSA)
 * phenoxybenzamine (in hypertension)
 * phentolamine (in hypertensive emergencies)
 * prazosin* (in hypertension)
 * tamsulosin (in BPH)
 * terazosin (in BPH and hypertension)
 * doxazocin* (in BPH and hypertension)

* denotes selective agonists to the receptor.

Subtypes
There are 3 α1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation.