Alpha-1 adrenergic receptor

The alpha-1 (α1) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptor in the central and peripheral nervous systems.

Effects
The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own.

General
Common (or still unspecified) effects include:
 * Vasoconstriction of arteries to heart (coronary arteries)
 * Venoconstriction 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-adrenergic 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 the pale appearance of the skin of an individual when frightened.

It also induces contraction of the urinary bladder, although this effect is minor compared to the relaxing effect of β2-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, except for the sphincters
 * Blood vessels of erectile tissue

Neuronal
Activation of α1-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity. Norepinephrine has been shown to decrease cellular excitability in all layers of the temporal cortex, including the primary auditory cortex. In particular, norepinephrine decreases glutamatergic excitatory postsynaptic potentials by the activation of α1-adrenergic receptors.

Other

 * Positive inotropic effect on heart muscle (α1<<β1) (in other words, strengthening the force of contraction)
 * 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

Signaling cascade
α1-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 further effects, primarily through the activation of an enzyme Protein Kinase C. This enzyme, as a kinase, functions by phosphorylation of other enzymes causing their activation, or by phosphorylation of certain channels leading to the increase or decrease of electrolyte transfer in or out of the cell.

Activity during exercise
During exercise these α1-adrenergic receptors can be selectively blocked by sympathetic nervous activity, allowing the β2-adrenergic receptors (which mediate vasodilation) to dominate. Note that only the α1-adrenergic receptors in active muscle will be blocked. Resting muscle will not have its α1-adrenergic receptors blocked, and hence the overall effect will be α1-adrenergic-mediated vasoconstriction.

Ligands

 * Agonists
 * Cirazoline
 * Etilefrine
 * Metaraminol
 * Methoxamine
 * Midodrine
 * Modafinil
 * Naphazoline
 * Oxymetazoline
 * Phenylephrine (decongestant)
 * Synephrine
 * Tetrahydrozoline
 * Xylometazoline


 * Antagonists
 * Alfuzosin (used in benign prostatic hyperplasia
 * Arotinolol
 * Carvedilol (used in congestive heart failure; it is a non-selective beta blocker)
 * Doxazosin (used in hypertension and benign prostatic hyperplasia)
 * Indoramin
 * Labetalol (used in hypertension; it is a mixed alpha/beta adrenergic antagonist)
 * Moxisylyte
 * Phenoxybenzamine
 * Phentolamine (used in hypertensive emergencies; it is a nonselective alpha-antagonist)
 * Prazosin (used in hypertension)
 * Silodosin
 * Tamsulosin (used in benign prostatic hyperplasia)
 * Terazosin
 * Tolazoline
 * Trimazosin

Various heterocyclic antidepressants and antipsychotics are α1-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediates side effects like orthostatic hypotension.