What is that
Norepinephrine, or norepinephrine if you prefer, is a hormone synthesized in the inner portion (medullary) of the adrenal gland, as well as a neurotransmitter produced by the central and peripheral nervous system. Most of the circulating norepinephrine comes from the nerve endings, while at the adrenal level it is mainly synthesized adrenaline (90% of adrenal medullary cells are specialized in its synthesis).
Norepinephrine is released in an important and superphysiological manner in response to severe physical or psychological stress, such as major bleeding, reduced blood glucose concentrations, traumatic wounds, surgery or fearful experiences.
Once secreted and released into the circulation, norepinephrine accelerates the heart rate, increases the release of glucose from energy reserves and increases blood flow to skeletal muscles. In synergy with epinephrine, norepinephrine prepares the body for the so-called "attack or flight" reaction, rapidly increasing metabolism and the ability to sustain a violent physical effort. Besides acting as a hormone, noradrenaline is a neurotransmitter characteristic of the central and sympathetic nervous systems; as such it is released by noradregenic neurons during synaptic transmission.
Noradrenaline is synthesized starting from tyrosine: the first reaction is the oxidation of the amino acid into dihydroxyphenylalanine (L-DOPA), followed by decarboxylation in the neurotransmitter dopamine and by β-oxidation in norepinephrine.
Functions
The effects in norepinephrine are concentrated mainly on the cardiovascular level. Its ability to increase cardiac frequency and contractility is well known, raising arterial pressure due to arteriolar cutaneous, genital, splacnica and renal vasoconstriction. Among the other actions of norepinephrine we recall the stimulating effect on the contraction of the sphincters, on dilation of the pupil and on sweating, while at metabolic level it promotes glycogenolysis, gluconeogenesis and lipolysis, decreasing insulin secretion and increasing that of glucagon.
receptors
To perform its biological effects, norepinephrine must interact with specific receptors, the so-called adrenergic receptors. Two types are essentially recognized, α and Β, with various subtypes for each class; the different expression of these receptors and their isoforms influences adrenergic activities at tissue level.
| Recet. | Sensitivity | Headquarters | Main actions of the agonists |
| α1 | Noradrenaline> adrenaline | Most target tissues | Smooth muscle contraction, with hypertensive effect |
| α2 | Adrenaline ≥ Noradrenaline | Gastrointestinal tract and pancreas | Smooth muscle contraction, decreased insulin secretion and increased glucagon, inhibited release of neurotransmitters (decreased production of noradrenaline and acetylcholine), contraction of the sphincters of the gastrointestinal tract |
| β1 | Adrenaline = Noradrenaline | Cardiac muscle, kidney | Increased contraction and heart rate, increased renin release, lipolysis stimulation in adipose tissue |
| β2 | Adrenaline > Noradrenaline | Some blood vessels and smooth muscle of some organs (bronchial smooth muscle, gastrointestinal, coronary) and large vessels supplying the skeletal musculature | Vasodilation, stimulation of lipolysis, anabolism and vasodilation in the muscle, with increased physical performance, stimulation of glycolysis and gluconeogenesis, increased renin secretion, sphincter contraction of the gastrointestinal tract |
| β3 | Norepinephrine > adrenaline | Adipose tissue | Stimulus on lipolysis |
Drugs and Supplements
Due to its ability to increase the release of fatty acids from adipose deposits, through the activation of beta-3-receptors, and to activate their metabolism at the level of peripheral tissues, with stimulation of thermogenesis, norepinephrine could be used for this purpose therapeutic to promote weight loss. In reality this practice is not carried out because the risks would exceed the benefits; noradrenaline is used instead in emergency therapy in the face of episodes of severe hypotension, septic shock and cardiogenic shock. Many slimming supplements, such as caffeine, the now-banned ephedrine, synephrine and the drugs that contain them (guarana, maté, coffee, tea, cola, ephedra, bitter orange), trace the effects of norepinephrine freeing it from neuronal vesicles and / or by binding to its receptors and stimulating them.
In the treatment of depression, instead, the so-called drugs that inhibit the serotonin and noradrenaline reuptake are used, which increase the concentrations available in the synapses, improving the level of communication between nerve cells. For the aforementioned constrictive effects of adrenaline at the level of the sphincters of the digestive and excretory tract, the same drugs can be used in the treatment of stress urinary incontinence.
