Slc6a2

Summary

Gene Symbol: Slc6a2
Description: solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2
Alias: NE-T, NET, Slc6a5, sodium-dependent noradrenaline transporter, NE transporter, norepinephrine transporter, solute carrier family 6 member 2
Species: mouse
Products:     Slc6a2

Top Publications

  1. Ren Z, Porzgen P, Zhang J, Chen X, Amara S, Blakely R, et al. Autocrine regulation of norepinephrine transporter expression. Mol Cell Neurosci. 2001;17:539-50 pubmed
    The norepinephrine transporter (NET) is a neurotransmitter scavenger and site of drug action in noradrenergic neurons...
  2. Hall F, Li X, Randall Thompson J, Sora I, Murphy D, Lesch K, et al. Cocaine-conditioned locomotion in dopamine transporter, norepinephrine transporter and 5-HT transporter knockout mice. Neuroscience. 2009;162:870-80 pubmed publisher
    ..by gene knockout (KO) of the dopamine transporter (DAT), the serotonin transporter (SERT) and the norepinephrine transporter (NET)...
  3. Haller J, Bakos N, Rodriguiz R, Caron M, Wetsel W, Liposits Z. Behavioral responses to social stress in noradrenaline transporter knockout mice: effects on social behavior and depression. Brain Res Bull. 2002;58:279-84 pubmed
    Noradrenaline has been implicated in the pathogenesis of depression and the noradrenaline transporter (NET) is a target for some antidepressants...
  4. Gilsbach R, Faron Górecka A, Rogoz Z, Bruss M, Caron M, Dziedzicka Wasylewska M, et al. Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors. J Neurochem. 2006;96:1111-20 pubmed
    The norepinephrine transporter (NET) is responsible for the rapid removal of norepinephrine released from sympathetic neurons; this release is controlled by inhibitory alpha(2)-adrenergic receptors (alpha(2)ARs)...
  5. Fritz J, Jayanthi L, Thoreson M, Blakely R. Cloning and chromosomal mapping of the murine norepinephrine transporter. J Neurochem. 1998;70:2241-51 pubmed
    ..regulation, and potential associations with complex behavioral trait loci, we amplified a mouse norepinephrine transporter (mNET) cDNA from placenta total RNA and utilized mNET probes to isolate and characterize the mNET gene...
  6. Morón J, Brockington A, Wise R, Rocha B, Hope B. Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci. 2002;22:389-95 pubmed
    Selective blockers of the norepinephrine transporter (NET) inhibit dopamine uptake in the prefrontal cortex. This suggests that dopamine in this region is normally cleared by the somewhat promiscuous NET...
  7. Mead A, Rocha B, Donovan D, Katz J. Intravenous cocaine induced-activity and behavioural sensitization in norepinephrine-, but not dopamine-transporter knockout mice. Eur J Neurosci. 2002;16:514-20 pubmed
    Previously, it was reported that both norepinephrine transporter (NET) and dopamine transporter (DAT) knockout (KO) mice were sensitive to the reinforcing effects of cocaine...
  8. Hall F, Li X, Sora I, Xu F, Caron M, Lesch K, et al. Cocaine mechanisms: enhanced cocaine, fluoxetine and nisoxetine place preferences following monoamine transporter deletions. Neuroscience. 2002;115:153-61 pubmed
    ..To test these ideas, drugs that block serotonin transporter (fluoxetine), norepinephrine transporter (nisoxetine) or all three transporters (cocaine) were examined in single- or multiple-transporter ..
  9. Rommelfanger K, Weinshenker D, Miller G. Reduced MPTP toxicity in noradrenaline transporter knockout mice. J Neurochem. 2004;91:1116-24 pubmed
    ..mice that exhibit elevated synaptic noradrenaline (NA) by genetically deleting the noradrenaline transporter (NET), a key regulator of the noradrenergic system (NET KO mice)...

More Information

Publications48

  1. Keller N, Diedrich A, Appalsamy M, Tuntrakool S, Lonce S, Finney C, et al. Norepinephrine transporter-deficient mice exhibit excessive tachycardia and elevated blood pressure with wakefulness and activity. Circulation. 2004;110:1191-6 pubmed
    ..is a primary neurotransmitter of central autonomic regulation and sympathetic nerve conduction, and the norepinephrine transporter (NET) is crucial in limiting catecholaminergic signaling...
  2. Ren Z, Pörzgen P, Youn Y, Sieber Blum M. Ubiquitous embryonic expression of the norepinephrine transporter. Dev Neurosci. 2003;25:1-13 pubmed
    We report that the norepinephrine transporter (NET) is expressed in avian and mouse embryos by numerous tissues that are derived from all three germ layers...
  3. Vizi E, Zsilla G, Caron M, Kiss J. Uptake and release of norepinephrine by serotonergic terminals in norepinephrine transporter knock-out mice: implications for the action of selective serotonin reuptake inhibitors. J Neurosci. 2004;24:7888-94 pubmed
    ..the functional properties of the noradrenergic system in genetically modified mice lacking the norepinephrine transporter (NET)...
  4. Xu F, Gainetdinov R, Wetsel W, Jones S, Bohn L, Miller G, et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci. 2000;3:465-71 pubmed
    ..NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants...
  5. Hall F, Schwarzbaum J, Perona M, Templin J, Caron M, Lesch K, et al. A greater role for the norepinephrine transporter than the serotonin transporter in murine nociception. Neuroscience. 2011;175:315-27 pubmed publisher
    ..and serotonin involvement in nociceptive functions is supported by observations of analgesic effects of norepinephrine transporter (NET) and serotonin transporter (SERT) inhibitors such as amitriptyline...
  6. Keller N, Diedrich A, Appalsamy M, Miller L, Caron M, McDonald M, et al. Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension. Neuroscience. 2006;139:931-46 pubmed
    ..The norepinephrine transporter is crucial in limiting catecholaminergic signaling...
  7. Perona M, Waters S, Hall F, Sora I, Lesch K, Murphy D, et al. Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions. Behav Pharmacol. 2008;19:566-74 pubmed publisher
    ..actions and many of their side effects via blockade of the plasma membrane transporters for serotonin (SERT/SLC6A2), norepinephrine (NET/SLC6A1), and dopamine (DAT/SLC6A3)...
  8. Haenisch B, Bilkei Gorzo A, Caron M, Bonisch H. Knockout of the norepinephrine transporter and pharmacologically diverse antidepressants prevent behavioral and brain neurotrophin alterations in two chronic stress models of depression. J Neurochem. 2009;111:403-16 pubmed publisher
    ..of ADs or genetic manipulations that produce antidepressant-like effects such as the knockout of the norepinephrine transporter (NET) gene...
  9. Wang Y, Xu F, Gainetdinov R, Caron M. Genetic approaches to studying norepinephrine function: knockout of the mouse norepinephrine transporter gene. Biol Psychiatry. 1999;46:1124-30 pubmed
    ..The norepinephrine transporter functions by uptaking norepinephrine back into the cell for cyclic use, and is a direct target of a ..
  10. Shirey Rice J, Klar R, FENTRESS H, Redmon S, Sabb T, Krueger J, et al. Norepinephrine transporter variant A457P knock-in mice display key features of human postural orthostatic tachycardia syndrome. Dis Model Mech. 2013;6:1001-11 pubmed publisher
    ..identified a mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2) in POTS patients...
  11. Jasmin L, Tien D, Weinshenker D, Palmiter R, Green P, Janni G, et al. The NK1 receptor mediates both the hyperalgesia and the resistance to morphine in mice lacking noradrenaline. Proc Natl Acad Sci U S A. 2002;99:1029-34 pubmed
    ..We conclude that when unopposed by NA, substance P acting at the NK1 receptor causes chronic thermal hyperalgesia, and that the reduced opioid efficacy associated with a lack of NA is due to increased NK1-receptor stimulation. ..
  12. Bennett B, Carosone Link P, Zahniser N, Johnson T. Confirmation and fine mapping of ethanol sensitivity quantitative trait loci, and candidate gene testing in the LXS recombinant inbred mice. J Pharmacol Exp Ther. 2006;319:299-307 pubmed
    ..Finally, we present an approach for using these RI strains to assess evidence for candidate genes in the narrowed intervals, and we apply this method to a strong candidate, the serotonin transporter. ..
  13. Parker L, Shanks J, Kennard J, Brain K. Dynamic monitoring of NET activity in mature murine sympathetic terminals using a fluorescent substrate. Br J Pharmacol. 2010;159:797-807 pubmed publisher
    To validate a fluorescence approach for monitoring norepinephrine transporter (NET) transport rate in mature sympathetic terminals, and to determine how prejunctional muscarinic receptors affect NET rate...
  14. Hong S, Lardaro T, Oh M, Huh Y, Ding Y, Kang U, et al. Regulation of the noradrenaline neurotransmitter phenotype by the transcription factor AP-2beta. J Biol Chem. 2008;283:16860-7 pubmed publisher
    ..In summary, we propose that AP-2beta plays critical and distinctive roles in the NA phenotype specification in both the peripheral and central nervous system during development. ..
  15. Harikrishnan K, Bayles R, Ciccotosto G, Maxwell S, Cappai R, Pelka G, et al. Alleviating transcriptional inhibition of the norepinephrine slc6a2 transporter gene in depolarized neurons. J Neurosci. 2010;30:1494-501 pubmed publisher
    ..Depolarized mouse neuronal cortical cells were examined for increased Slc6a2 mRNA synthesis, changes in CpG methylation status using bisulfite sequencing, and binding of MeCP2 and Smarca2 on ..
  16. Li Z, Caron M, Blakely R, Margolis K, Gershon M. Dependence of serotonergic and other nonadrenergic enteric neurons on norepinephrine transporter expression. J Neurosci. 2010;30:16730-40 pubmed publisher
    The norepinephrine transporter (NET), which is expressed on the plasma membranes of noradrenergic neurons, is important in terminating neurotransmission...
  17. Gallagher J, Zhang X, Hall F, Uhl G, Bearer E, Jacobs R. Altered reward circuitry in the norepinephrine transporter knockout mouse. PLoS ONE. 2013;8:e57597 pubmed publisher
    ..This work concentrates on the norepinephrine transporter (NET), using a battery of in vivo magnetic resonance imaging techniques and histological correlates to ..
  18. Yao W, Gainetdinov R, Arbuckle M, Sotnikova T, Cyr M, Beaulieu J, et al. Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron. 2004;41:625-38 pubmed
    ..Our findings uncover a previously unappreciated role of PSD-95 in psychostimulant action and identify a molecular and cellular mechanism shared between drug-related plasticity and learning. ..
  19. Jiang W, Prokopenko O, Wong L, Inouye M, Mirochnitchenko O. IRIP, a new ischemia/reperfusion-inducible protein that participates in the regulation of transporter activity. Mol Cell Biol. 2005;25:6496-508 pubmed
    ..On the basis of these results, we propose that IRIP regulates the activity of a variety of transporters under normal and pathological conditions. ..
  20. Haughey H, Kaiser A, Johnson T, Bennett B, Sikela J, Zahniser N. Norepinephrine transporter: a candidate gene for initial ethanol sensitivity in inbred long-sleep and short-sleep mice. Alcohol Clin Exp Res. 2005;29:1759-68 pubmed
    ..molecular biological, neurochemical, and behavioral approaches were used to test the hypothesis that the norepinephrine transporter (NET) contributes to the differences in ethanol-induced loss of righting reflex (LORR) in ILS and ISS ..
  21. Genestine M, Lin L, Durens M, Yan Y, Jiang Y, Prem S, et al. Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior. Hum Mol Genet. 2015;24:5805-27 pubmed publisher
    ..These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders. ..
  22. Solich J, Kolasa M, Kusmider M, Faron Górecka A, Pabian P, Zurawek D, et al. Norepinephrine transporter knock-out alters expression of the genes connected with antidepressant drugs action. Brain Res. 2015;1594:284-92 pubmed publisher
    b>Norepinephrine transporter knock-out mice (NET-KO) exhibit depression-resistant phenotypes. They manifest significantly shorter immobility times in both the forced swim test and the tail suspension test...
  23. Markel P, Bennett B, Beeson M, Gordon L, Johnson T. Confirmation of quantitative trait loci for ethanol sensitivity in long-sleep and short-sleep mice. Genome Res. 1997;7:92-9 pubmed
    ..This represents the first report of linkages for genes influencing alcohol action in any mammalian system using stringent, genome-wide mapping criteria. ..
  24. Shields A, Wang Q, Winder D. alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009;163:339-51 pubmed publisher
    ..this expression is more similar in distribution to the vesicular glutamate transporters than to either norepinephrine transporter or tyrosine hydroxylase positive terminals...
  25. Hu Y, Caron M, Sieber Blum M. Norepinephrine transport-mediated gene expression in noradrenergic neurogenesis. BMC Genomics. 2009;10:151 pubmed publisher
    ..a differential gene expression profile in neural crest stem cells that is due to deletion of the norepinephrine transporter (NET) gene...
  26. Wei H, Hill E, Gu H. Functional mutations in mouse norepinephrine transporter reduce sensitivity to cocaine inhibition. Neuropharmacology. 2009;56:399-404 pubmed publisher
    ..We have performed several rounds of random and site-directed mutagenesis in the mouse norepinephrine transporter and screened for mutants with altered sensitivity to cocaine inhibition of substrate uptake...
  27. Sucic S, Bryan Lluka L. The role of the conserved GXXXRXG motif in the expression and function of the human norepinephrine transporter. Brain Res Mol Brain Res. 2002;108:40-50 pubmed
    Highly conserved motifs in the monoamine transporters, e.g. the human norepinephrine transporter (hNET) GXXXRXG motif which was the focus of the present study, are likely to be important structural features in determining function...
  28. Bohn L, Xu F, Gainetdinov R, Caron M. Potentiated opioid analgesia in norepinephrine transporter knock-out mice. J Neurosci. 2000;20:9040-5 pubmed
    ..effects of TCAs are determined by their ability to inhibit norepinephrine reuptake via interactions with the NET. To test this idea, we studied mice lacking a functional NET in spontaneous and morphine-induced antinociceptive ..
  29. Ramachandran B, Houben K, Rozenberg Y, Haigh J, Varpetian A, Howard B. Differential expression of transporters for norepinephrine and glutamate in wild type, variant, and WNT1-expressing PC12 cells. J Biol Chem. 1993;268:23891-7 pubmed
    Wild type PC12 pheochromocytoma cells express a Na(+)-dependent norepinephrine transporter that operates in the uptake of catecholamines, including dopamine...
  30. Mannangatti P, NarasimhaNaidu K, DAMAJ M, Ramamoorthy S, Jayanthi L. A Role for p38 Mitogen-activated Protein Kinase-mediated Threonine 30-dependent Norepinephrine Transporter Regulation in Cocaine Sensitization and Conditioned Place Preference. J Biol Chem. 2015;290:10814-27 pubmed publisher
    ..Previously, we demonstrated a role for p38 MAPK-mediated norepinephrine transporter (NET) Thr(30) phosphorylation in cocaine-induced NET up-regulation (Mannangatti, P., Arapulisamy, O...
  31. Pirzgalska R, Seixas E, Seidman J, Link V, Sánchez N, Mahú I, et al. Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nat Med. 2017;23:1309-1318 pubmed publisher
    ..macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme...
  32. Martillotti J, Weinshenker D, Liles L, Eagles D. A ketogenic diet and knockout of the norepinephrine transporter both reduce seizure severity in mice. Epilepsy Res. 2006;68:207-11 pubmed
    ..By contrast, knockout of the NE transporter (NET) gene, which elevates synaptic levels of norepinephrine, decreases seizure severity in mice fed normal ..
  33. Höglund P, Adzic D, Scicluna S, Lindblom J, Fredriksson R. The repertoire of solute carriers of family 6: identification of new human and rodent genes. Biochem Biophys Res Commun. 2005;336:175-89 pubmed
    ..This paper presents an overall overview of the gene repertoire of the SLC6 gene family and its expression profile in rats. ..
  34. Mebel D, Wong J, Dong Y, Borgland S. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur J Neurosci. 2012;36:2336-46 pubmed publisher
    ..Taken together, these results indicate that insulin depresses DA concentration in the VTA via increased reuptake of DA through DAT. Insulin-mediated decrease of DA in the VTA may suppress salience of food once satiety is reached. ..
  35. Dluzen D, Park J, Kim K. Modulation of olfactory bulb tyrosine hydroxylase and catecholamine transporter mRNA by estrogen. Brain Res Mol Brain Res. 2002;108:121-8 pubmed
    ..the olfactory bulbs were assayed for mRNA levels of tyrosine hydroxylase, dopamine transporter and norepinephrine transporter using competitive-PCR...
  36. Solich J, Kolasa M, Kusmider M, Pabian P, Faron Górecka A, Zurawek D, et al. Life-long norepinephrine transporter (NET) knock-out leads to the increase in the NET mRNA in brain regions rich in norepinephrine terminals. Eur Neuropsychopharmacol. 2015;25:1099-108 pubmed publisher
    ..aimed to identify the genes differentially expressed in the frontal cortex of mice bearing a life-long norepinephrine transporter knock-out (NET-KO) and wild-type animals (WT)...
  37. Siuta M, Robertson S, KOCALIS H, Saunders C, Gresch P, Khatri V, et al. Dysregulation of the norepinephrine transporter sustains cortical hypodopaminergia and schizophrenia-like behaviors in neuronal rictor null mice. PLoS Biol. 2010;8:e1000393 pubmed publisher
    ..elevated cortical norepinephrine (NE), unaltered cortical serotonin (5-HT), and enhanced expression of the NE transporter (NET). In the cortex, NET takes up both extracellular NE and DA...
  38. Ma Y, Krueger J, Redmon S, Uppuganti S, Nyman J, Hahn M, et al. Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis. J Biol Chem. 2013;288:30105-13 pubmed publisher
    ..We show here that differentiated osteoblasts, like neurons, express the norepinephrine transporter (NET), exhibit specific NE uptake activity via NET and can catabolize, but not generate, NE...
  39. Gupta S, Sharma B, Singh P, Sharma B. Modulation of transient receptor potential vanilloid subtype 1 (TRPV1) and norepinephrine transporters (NET) protect against oxidative stress, cellular injury, and vascular dementia. Curr Neurovasc Res. 2014;11:94-106 pubmed
    ..Selective norepinephrine transporter (NET) inhibitors have a role in cognitive dysfunction and oxidative stress...