Noradrenaline

What is that

Norepinephrine, or norepinephrine if you prefer, is a hormone synthesized in the internal (medullary) portion of the adrenal gland, as well as a neurotransmitter produced by the central and peripheral nervous system. Most of the circulating norepinephrine comes from nerve endings, while adrenal is mainly synthesized adrenaline (90% of the cells of the adrenal medulla are specialized in its synthesis).

Norepinephrine is released in an important and supraphysiological way in response to severe physical or psychological stress, such as "major bleeding, a reduction in blood glucose concentrations, traumatic wounds, surgery or fearful experiences.

Once secreted and released into the circulation, norepinephrine accelerates heart rate, increases the release of glucose from energy stores and increases blood flow to skeletal muscles. In synergy with epinephrine, noradrenaline prepares the body for the so-called "fight or flight" reaction, rapidly increasing the metabolism and the ability to sustain a violent physical effort. In addition to acting as a hormone, noradrenaline is a characteristic neurotransmitter of the central and sympathetic nervous systems; as such it is released by noradregenic neurons during synaptic transmission.

Norepinephrine is synthesized from tyrosine: the first reaction is the oxidation of the amino acid into dihydroxyphenylalanine (L-DOPA), followed by decarboxylation into the neurotransmitter dopamine and β-oxidation into noradrenaline.

Functions

The effects in norepinephrine are mainly concentrated at the cardiovascular level. Its ability to increase heart rate and contractility is well known, raising blood pressure due to cutaneous, genital, splacnic and renal arteriolar vasoconstriction. Among the other actions of noradrenaline we remember the stimulating effect on the contraction of the sphincters, on the dilation of the pupil and on sweating, while at the metabolic level it promotes glycogenolysis, gluconeogenesis and lipolysis, decreasing the secretion of insulin and increasing that of glucagon.

As shown in the figure (click on the image to enlarge), the stimuli necessary to produce consistent increases of norepinephrine in the blood have a much higher intensity and stressogenic power than those that raise adrenaline.

Receptors

To carry out its biological effects, norepinephrine must interact with specific receptors, the so-called adrenergic receptors. There are essentially two types, α and Β, with various subtypes for each class; the different expression of these receptors and of the relative isoforms influences the adrenergic activities at the 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 neurotransmitter release (decreased production of norepinephrine and acetylcholine), contraction of the gastrointestinal tract sphincters β1 Adrenaline
= Noradrenaline Cardiac muscle, kidney Increased contraction and heart rate, increased release of renin, stimulation of lipolysis in adipose tissue β2 Adrenaline
> Noradrenaline Certain blood vessels and smooth muscle of certain organs (bronchial, gastrointestinal, coronary smooth muscles) and large vessels supplying skeletal muscles Vasodilation, stimulation of lipolysis, anabolism and vasodilation in the muscles, with increase in physical performance, stimulation of glycolysis and gluconeogenesis, increased secretion of renin, contraction of the sphincters of the gastrointestinal tract β3 Noradrenaline
> adrenaline Adipose tissue Stimulus on lipolysis

Medicines 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 peripheral tissue level, with stimulation on thermogenesis, noradrenaline could be used for the purpose therapeutic to promote weight loss. In reality this practice is not carried out because the risks would outweigh the benefits, noradrenaline is instead used 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, on the other hand, so-called serotonin and noradrenaline reuptake inhibitors are used, which increase the concentrations available in the synapses by improving the level of communication between nerve cells. For the aforementioned constricting effects of adrenaline on the level of the sphincters of the digestive and excretory systems, the same drugs can be used in the treatment of stress urinary incontinence.