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Pathway Description
Norepinephrine Neurological
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2023-09-22
Last Updated: 2024-01-21
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin ad, "near", and ren, "kidney") is more commonly used in the United Kingdom, whereas "norepinephrine" (from Ancient Greek ἐπῐ́ (epí), "upon", and νεφρός (nephrós), "kidney") is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic. The general function of norepinephrine is to mobilize the brain and body for action. 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. In the brain, norepinephrine increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention; it also increases restlessness and anxiety. 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. In the brain, noradrenaline is produced in nuclei that are small yet exert powerful effects on other brain areas. The most important of these nuclei is the locus coeruleus, located in the pons. Outside the brain, norepinephrine is used as a neurotransmitter by sympathetic ganglia located near the spinal cord or in the abdomen, as well as Merkel cells located in the skin. It is also released directly into the bloodstream by the adrenal glands. 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. Norepinephrine is a catecholamine and a phenethylamine. 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. 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. 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. In mammals, norepinephrine is rapidly degraded to various metabolites. The initial step in the breakdown can be catalyzed by either of the enzymes monoamine oxidase (mainly monoamine oxidase A) or COMT. From there, the breakdown can proceed by a variety of pathways. 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.[13]
References
Norepinephrine Neurological References
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Albert VR, Lee MR, Bolden AH, Wurzburger RJ, Aguanno A: Distinct promoters direct neuronal and nonneuronal expression of rat aromatic L-amino acid decarboxylase. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12053-7. doi: 10.1073/pnas.89.24.12053.
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Grima B, Lamouroux A, Blanot F, Biguet NF, Mallet J: Complete coding sequence of rat tyrosine hydroxylase mRNA. Proc Natl Acad Sci U S A. 1985 Jan;82(2):617-21. doi: 10.1073/pnas.82.2.617.
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Haycock JW, Haycock DA: Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes. J Biol Chem. 1991 Mar 25;266(9):5650-7.
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Bevilaqua LR, Graham ME, Dunkley PR, von Nagy-Felsobuki EI, Dickson PW: Phosphorylation of Ser(19) alters the conformation of tyrosine hydroxylase to increase the rate of phosphorylation of Ser(40). J Biol Chem. 2001 Nov 2;276(44):40411-6. doi: 10.1074/jbc.M105280200. Epub 2001 Aug 13.
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Chu PJ, Best PM: Molecular cloning of calcium channel alpha(2)delta-subunits from rat atria and the differential regulation of their expression by IGF-1. J Mol Cell Cardiol. 2003 Feb;35(2):207-15.
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This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0122188
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