Norepinephrine transporter
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2008-07-08T01:27:23Z
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The '''[[norepinephrine]] transporter''' or '''NET''' (or noradrenaline transporter (NAT)) is a [[monoamine transporter]] that transports the [[neurotransmitter]] [[noradrenaline]] from the [[synapse]] back to its vesicles for storage until later use. It also appears to transport the [[neurotransmitter]] [[dopamine]] in the same way, but to a lesser degree. "The norepinephrine transporter (NET) protein consists of 617 amino acids and has 12 transmembrane domains"<ref>[http://www-ermm.cbcu.cam.ac.uk/01003891h.htm Tahir Tellioglu and David Robertson, The molecular structure of the norepinephrine transporter protein.]</ref> and is encoded by the '''{{gene|SLC6A2}}''' [[gene]].
Certain [[antidepressant]] medications act to raise noradrenaline, such as the [[SNRI]]s and the [[tricyclic antidepressants]] (TCAs). In other words, these medications prevent the noradrenaline transporter from doing its job. Noradrenaline therefore remains in the [[synapse]] longer, allowing it to reach more normal levels. Since the noradrenaline transporter is also thought to transport dopamine to some extent, [[SNRI]]s would also raise dopamine levels in the synapse.
A loss of function mutation in the noradrenaline transporter has been associated with [[postural orthostatic tachycardia syndrome]] in one kindred.<ref>{{cite journal |author=Shannon J, Flattem N, Jordan J, Jacob G, Black B, Biaggioni I, Blakely R, Robertson D |title=Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency |journal=N Engl J Med |volume=342 |issue=8 |pages=541–9 |year=2000 |pmid=10684912 |doi=10.1056/NEJM200002243420803}}</ref> An [[epigenetic]] mechanism (hypermethylation of CpG islands in the NET gene promoter region)<ref>{{cite journal |author=Esler M, Alvarenga M, Pier C, Richards J, El-Osta A, Barton D, Haikerwal D, Kaye D, Schlaich M, Guo L, Jennings G, Socratous F, Lambert G |title=The neuronal noradrenaline transporter, anxiety and cardiovascular disease |journal=J Psychopharmacol |volume=20 |issue=4 Suppl |pages=60–6 |year=2006 |pmid=16785272 |doi=10.1177/1359786806066055}}</ref> that results in reduced expression of the noradrenaline transporter and consequently a phenotype of impaired neuronal reuptake of [[noradrenaline]] has been implicated in both postural orthostatic tachycardia syndrome and [[panic disorder]].
<blockquote>"The involvement of the norepinephrine transporter (NET) in the [[pathophysiology]] and treatment of [[attention deficit hyperactivity disorder]] (ADHD), [[substance abuse]], neurodegenerative disorders (e.g., [[Alzheimer's disease]] (AD) and [[Parkinson's disease]] (PD)) and [[clinical depression]] has long been recognized. [2006]"<ref>[http://www.ihop-net.org/UniPub/iHOP/bng/92208.html Information Hyperlinked Over Proteins (IHOP)]</ref>
</blockquote>
==See also==
*[[Neurotransmitter transporter]]
* [[Sodium:neurotransmitter symporter]]
* [[Solute carrier family]]
==References==
<references/>
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal | author=Eisenhofer G |title=The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. |journal=Pharmacol. Ther. |volume=91 |issue= 1 |pages= 35–62 |year= 2001 |pmid= 11707293 |doi= }}
*{{cite journal | author=Pacholczyk T, Blakely RD, Amara SG |title=Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. |journal=Nature |volume=350 |issue= 6316 |pages= 350–4 |year= 1991 |pmid= 2008212 |doi= 10.1038/350350a0 }}
*{{cite journal | author=Pörzgen P, Bönisch H, Brüss M |title=Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. |journal=Biochem. Biophys. Res. Commun. |volume=215 |issue= 3 |pages= 1145–50 |year= 1995 |pmid= 7488042 |doi= 10.1006/bbrc.1995.2582 }}
*{{cite journal | author=Gelernter J, Kruger S, Pakstis AJ, ''et al.'' |title=Assignment of the norepinephrine transporter protein (NET1) locus to chromosome 16. |journal=Genomics |volume=18 |issue= 3 |pages= 690–2 |year= 1994 |pmid= 7905857 |doi= }}
*{{cite journal | author=Brüss M, Kunz J, Lingen B, Bönisch H |title=Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter. |journal=Hum. Genet. |volume=91 |issue= 3 |pages= 278–80 |year= 1993 |pmid= 8478011 |doi= }}
*{{cite journal | author=Pörzgen P, Bönisch H, Hammermann R, Brüss M |title=The human noradrenaline transporter gene contains multiple polyadenylation sites and two alternatively spliced C-terminal exons. |journal=Biochim. Biophys. Acta |volume=1398 |issue= 3 |pages= 365–70 |year= 1998 |pmid= 9655936 |doi= }}
*{{cite journal | author=Apparsundaram S, Schroeter S, Giovanetti E, Blakely RD |title=Acute regulation of norepinephrine transport: II. PKC-modulated surface expression of human norepinephrine transporter proteins. |journal=J. Pharmacol. Exp. Ther. |volume=287 |issue= 2 |pages= 744–51 |year= 1998 |pmid= 9808705 |doi= }}
*{{cite journal | author=Kim CH, Kim HS, Cubells JF, Kim KS |title=A previously undescribed intron and extensive 5' upstream sequence, but not Phox2a-mediated transactivation, are necessary for high level cell type-specific expression of the human norepinephrine transporter gene. |journal=J. Biol. Chem. |volume=274 |issue= 10 |pages= 6507–18 |year= 1999 |pmid= 10037744 |doi= }}
*{{cite journal | author=Shannon JR, Flattem NL, Jordan J, ''et al.'' |title=Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. |journal=N. Engl. J. Med. |volume=342 |issue= 8 |pages= 541–9 |year= 2000 |pmid= 10684912 |doi= }}
*{{cite journal | author=Torres GE, Yao WD, Mohn AR, ''et al.'' |title=Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. |journal=Neuron |volume=30 |issue= 1 |pages= 121–34 |year= 2001 |pmid= 11343649 |doi= }}
*{{cite journal | author=Gu HH, Wu X, Giros B, ''et al.'' |title=The NH(2)-terminus of norepinephrine transporter contains a basolateral localization signal for epithelial cells. |journal=Mol. Biol. Cell |volume=12 |issue= 12 |pages= 3797–807 |year= 2002 |pmid= 11739781 |doi= }}
*{{cite journal | author=Paczkowski FA, Bryan-Lluka LJ |title=Tyrosine residue 271 of the norepinephrine transporter is an important determinant of its pharmacology. |journal=Brain Res. Mol. Brain Res. |volume=97 |issue= 1 |pages= 32–42 |year= 2002 |pmid= 11744160 |doi= }}
*{{cite journal | author=Paczkowski FA, Bönisch H, Bryan-Lluka LJ |title=Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter. |journal=Pharmacogenetics |volume=12 |issue= 2 |pages= 165–73 |year= 2002 |pmid= 11875370 |doi= }}
*{{cite journal | author=Barr CL, Kroft J, Feng Y, ''et al.'' |title=The norepinephrine transporter gene and attention-deficit hyperactivity disorder. |journal=Am. J. Med. Genet. |volume=114 |issue= 3 |pages= 255–9 |year= 2002 |pmid= 11920844 |doi= }}
*{{cite journal | author=Zill P, Engel R, Baghai TC, ''et al.'' |title=Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression. |journal=Neuropsychopharmacology |volume=26 |issue= 4 |pages= 489–93 |year= 2002 |pmid= 11927173 |doi= 10.1016/S0893-133X(01)00386-4 }}
*{{cite journal | author=Leszczyńska-Rodziewicz A, Czerski PM, Kapelski P, ''et al.'' |title=A polymorphism of the norepinephrine transporter gene in bipolar disorder and schizophrenia: lack of association. |journal=Neuropsychobiology |volume=45 |issue= 4 |pages= 182–5 |year= 2002 |pmid= 12097806 |doi= }}
*{{cite journal | author=Bauman PA, Blakely RD |title=Determinants within the C-terminus of the human norepinephrine transporter dictate transporter trafficking, stability, and activity. |journal=Arch. Biochem. Biophys. |volume=404 |issue= 1 |pages= 80–91 |year= 2002 |pmid= 12127072 |doi= }}
*{{cite journal | author=Urwin RE, Bennetts B, Wilcken B, ''et al.'' |title=Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. |journal=Mol. Psychiatry |volume=7 |issue= 6 |pages= 652–7 |year= 2003 |pmid= 12140790 |doi= 10.1038/sj.mp.4001080 }}
*{{cite journal | author=McEvoy B, Hawi Z, Fitzgerald M, Gill M |title=No evidence of linkage or association between the norepinephrine transporter (NET) gene polymorphisms and ADHD in the Irish population. |journal=Am. J. Med. Genet. |volume=114 |issue= 6 |pages= 665–6 |year= 2003 |pmid= 12210284 |doi= 10.1002/ajmg.10416 }}
}}
{{refend}}
==External links==
* {{MeshName|Norepinephrine+transporter}}
{{neuroscience-stub}}
{{Membrane transport proteins}}
{{Neurotransmitter transporters}}
[[Category:Membrane biology]]
[[Category:Neurotransmitter transporters]]
[[Category:Solute carrier family]]
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