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.
The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own. α1-receptors primarily mediate smooth muscle contraction, but have important functions elsewhere as well. The hormone noradrenaline has higher affinity for the α1 recepter than does adrenaline.
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 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 β3-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 on smooth muscle are contraction in:
- 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:
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.
- Both positive and negative inotropic effects 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
- Activate mitogenic responses and regulate growth and proliferation of many cells
- Involved in the detection of mechanical feedback on the hypoglossal motor neurons which allow a long-term facilitation in respiration in response to repeated apneas.
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, α1-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β2-adrenergic receptors which mediate vasodilation to dominate. In contrast to α2-adrenergic receptors, α1-adrenergic-receptors in the arterial vasculature of skeletal muscle are more resistant to inhibition, and attenuation of α1-adrenergic-receptor-mediated vasoconstriction only occurs during heavy exercise.
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.
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, and headaches due to excessive vasodilation.