Norepinephrine

noradrenalinenoradrenergicnoradrenalinNEnoradrenergic activityadrenergiclevarterenollevophednoradrenaline (NA)noradrenaline receptors
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter.wikipedia
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Fight-or-flight response

stress responsefight or flightfight-or-flight
Norepinephrine release is lowest during sleep, rises during wakefulness, and reaches much higher levels during situations of stress or danger, in the so-called fight-or-flight response.
More specifically, the adrenal medulla produces a hormonal cascade that results in the secretion of catecholamines, especially norepinephrine and epinephrine.

Catecholamine

catecholaminescatecholamine synthesiscatecholamine systems
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter.
Included among catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine.

Locus coeruleus

locus ceruleuslocus coereuleuslocus coeruleus-noradrenergic system
The most important of these nuclei is the locus coeruleus, located in the pons.
The locus coeruleus is the principal site for brain synthesis of norepinephrine (noradrenaline).

Beta blocker

beta blockersbeta-blockersbeta-blocker
Beta blockers, which counter some of the effects of noradrenaline, are frequently used to treat glaucoma, migraine, and a range of cardiovascular problems.
Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response.

Heart rate

heartbeatresting heart ratemaximum heart rate
In the rest of the body, norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy stores, increases blood flow to skeletal muscle, reduces blood flow to the gastrointestinal system, and inhibits voiding of the bladder and gastrointestinal motility.
The accelerans nerve provides sympathetic input to the heart by releasing norepinephrine onto the cells of the sinoatrial node (SA node), and the vagus nerve provides parasympathetic input to the heart by releasing acetylcholine onto sinoatrial node cells.

Adrenal gland

adrenal glandsadrenalsuprarenal gland
Outside the brain, norepinephrine is used as a neurotransmitter by sympathetic ganglia located near the spinal cord or in the abdomen, and it is also released directly into the bloodstream by the adrenal glands.
The medulla produces the catecholamine, adrenaline and noradrenaline, which function to produce a rapid response throughout the body in stress situations.

Adrenal medulla

medullamedullary(medulla)
Norepinephrine is synthesized from the amino acid tyrosine by a series of enzymatic steps in the adrenal medulla and postganglionic neurons of the sympathetic nervous system.
It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine in response to stimulation by sympathetic preganglionic neurons.

Dopamine

dopaminergic systemDAdopaminergic
Thus the direct precursor of norepinephrine is dopamine, which is synthesized indirectly from the essential amino acid phenylalanine or the non-essential amino acid tyrosine.
In blood vessels, it inhibits norepinephrine release and acts as a vasodilator (at normal concentrations); in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes.

L-DOPA

levodopa L -DOPADOPA
Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O 2, and probably ferrous iron (Fe 2+ ) as cofactors.
-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines.

Tyrosine hydroxylase

THtyrosine 3-monooxygenasetyrosine
Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O 2, and probably ferrous iron (Fe 2+ ) as cofactors.
L -DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline).

Phenylethanolamine N-methyltransferase

phenylethanolamine ''N''-methyltransferasePNMTphenylethanolamine N-methyl transferase
Norepinephrine itself can further be converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl- L -methionine as cofactor.
Phenylethanolamine N-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline).

Sympathetic nervous system

sympatheticsympathetic nervesympathetic nerves
Norepinephrine is synthesized from the amino acid tyrosine by a series of enzymatic steps in the adrenal medulla and postganglionic neurons of the sympathetic nervous system.
In response to this stimulus, the postganglionic neurons release norepinephrine, which activates adrenergic receptors that are present on the peripheral target tissues.

Phenylalanine

PheL-phenylalaninephenylalanine metabolism
Thus the direct precursor of norepinephrine is dopamine, which is synthesized indirectly from the essential amino acid phenylalanine or the non-essential amino acid tyrosine.
Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the skin pigment melanin.

Adrenaline

epinephrineadrenaline junkieadrenalin
Norepinephrine itself can further be converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl- L -methionine as cofactor. Its structure differs from that of epinephrine only in that epinephrine has a methyl group attached to its nitrogen, whereas the methyl group is replaced by a hydrogen atom in norepinephrine.
The adrenal glands contribute about 7% of circulating noradrenaline, most of which is a spill over from neurotransmission with little activity as a hormone.

Tetrahydrobiopterin

BH4Sapropterinsapropterin dihydrochloride
Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O 2, and probably ferrous iron (Fe 2+ ) as cofactors. Phenylalanine is converted into tyrosine by the enzyme phenylalanine hydroxylase, with molecular oxygen (O 2 ) and tetrahydrobiopterin as cofactors.
Tetrahydrobiopterin (BH 4, THB), also known as sapropterin, is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases.

Brain

brain functionmammalian braincerebral
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone and neurotransmitter.
Norepinephrine, which is involved in arousal, comes exclusively from a nearby small area called the locus coeruleus.

Alpha-1 adrenergic receptor

α 1 α 1 -adrenergic receptorα 1 -adrenergic
Alpha receptors are divided into subtypes α 1 and α 2 ; beta receptors into subtypes β 1, β 2, and β 3.
Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α 1 -adrenergic receptor in the central and peripheral nervous systems.

Monoamine oxidase A

MAO-AMAOAMAO A
The initial step in the breakdown can be catalyzed by either of the enzymes monoamine oxidase (mainly monoamine oxidase A) or COMT.
This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin.

Adrenergic receptor

adrenergic receptorsβadrenergic
Regardless of how and where it is released, norepinephrine acts on target cells by binding to and activating adrenergic receptors located on the cell surface.
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, β 2 agonists and α 2 agonists, which are used to treat high blood pressure and asthma, for example.

Synaptic vesicle

synaptic vesiclesvesiclesvesicle
While the conversion of tyrosine to dopamine occurs predominantly in the cytoplasm, the conversion of dopamine to norepinephrine by dopamine β-monooxygenase occurs predominantly inside neurotransmitter vesicles.

Dopamine beta-hydroxylase

dopamine β-hydroxylaseDBHDopamine beta-monooxygenase
While the conversion of tyrosine to dopamine occurs predominantly in the cytoplasm, the conversion of dopamine to norepinephrine by dopamine β-monooxygenase occurs predominantly inside neurotransmitter vesicles.
The three substrates of this enzyme are Dopamine (3,4-dihydroxyphenethylamine), Vitamin C (ascorbate), and O 2, whereas its three products are noradrenaline, dehydroascorbate, and H 2 O.

Vesicular monoamine transporter

VMATvesicular amine transportervesicular monoamine transport proteins
After synthesis, norepinephrine is transported from the cytosol into synaptic vesicles by the vesicular monoamine transporter (VMAT).
Monoamines transported by VMATs are mainly noradrenaline, adrenaline, dopamine, serotonin, histamine, and trace amines.

3-Methoxy-4-hydroxyphenylglycol

methoxyhydroxyphenylglycolMHPG3,4-dihydroxyphenylethylglycol
The principal end products are either Vanillylmandelic acid or a conjugated form of MHPG, both of which are thought to be biologically inactive and are excreted in the urine.
3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG) is a metabolite of norepinephrine degradation.

Norepinephrine transporter

NETnorepinephrinenoradrenaline transporter
They are then absorbed back into the presynaptic cell, via reuptake mediated primarily by the norepinephrine transporter (NET).
NET is a monoamine transporter and is responsible for the sodium-chloride (Na + /Cl − )-dependent reuptake of extracellular norepinephrine (NE), which is also known as noradrenaline.

Vanillylmandelic acid

vanilmandelic acidvanillylmandelic acid (VMA)Vanillyl mandelic acid
The principal end products are either Vanillylmandelic acid or a conjugated form of MHPG, both of which are thought to be biologically inactive and are excreted in the urine.
Vanillylmandelic acid (VMA) is a chemical intermediate in the synthesis of artificial vanilla flavorings and is an end-stage metabolite of the catecholamines (dopamine, epinephrine, and norepinephrine).