Norepinephrine transporter transporters

Therefore, dopamine transporter inhibitors exhibit less effect in the FC. There, dopamine seems to be reuptaken by the norepinephrine transporter, which dopamine actually has a higher affinity for than norepinephrine itself. 

Bonisch, H, Hammermann, R and Bruss, M (1998) Role of protein kinase C and second messengers in regulation of the norepinephrine transporter. Adv. Pharmacol. 42 183-186. 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

Kim, C. H., Kim, H. S., Cubells, J. F., 8c Kim, K. S. (1999). 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. /. Biol. Chem., 274, 6507-18. 

Szot, R, Ashliegh, E. A., Kohen, R. etal. (1993). Norepinephrine transporter mRNA is elevated in the locus coeruleus following short- and long-term desipramine treatment. Brain Res., 618, 308-12. 

Yoshida, K., Takahashi, H., Higuchi, H. etal. (2004). Prediction of antidepressants response to milnacipran by norepinephrine transporter gene polymorphisms. Am. J. Psychiatry, 161(9), 1575-80. 

Zill, P., Engel, R., Baghai, T. C. etal. (2002). Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression. Neuropsychopharmacol, 26, 489-93. 

Basheer, R Magner, M., McCarley, R. W. Shiromani, P. J. (1998). REM sleep deprivation increases the levels of tyrosine hydroxylase and norepinephrine transporter mRNA in the locus coeruleus. Brain Res. Mol. Brain Res. 57,... 

Some less obvious phenomena of catecholamine transport and biosynthesis further illustrate the complexities of deciphering how efferents from midbrain dopamine neurons contribute to sleep-wake regulation. The plasma membrane norepinephrine transporter (NET), which is responsible for the uptake of extracellular noradrenaline, can also readily transport dopamine, and does so in vivo. This... 

Buck K., Amara S. Chimeric dopamine-norepinephrine transporters delineate structural domains influencing selectivity for catecholamines and l-methyl-4-phenylpyridinium. Proc. Natl. Acad. Sci. U.S.A. 91 12584, 1994. 

The neuronal membrane norepinephrine transporter (NET), the dopamine transporter (DAT) and the vesicular membrane transporter (VMAT-2), which is the same in all catecholamine-containing neurons, have similar numbers of predicted transmembrane segments. They have different numbers of amino acids, pharmacological properties and chromosomal localizations. 

C-termini and a large glycosylated extracellular loop between transmembrane domains 3 and 4. The proteins show the most homology in their transmembrane spanning domains, particularly domains 1, 2, and 4-8, which may be involved in moving the transmitter across the membrane. The transporters are substrates for PKC-dependent phosphorylation, which reduces their activity. The dopamine transporter is phosphorylated on the extreme end of the N-terminal tail, and consensus phosphorylation sites for various other kinases are present in the intracellular loops and domains [20-22] (Fig. 12-4). The dopamine and norepinephrine transporters form functional homo-oligomers, although it is not known if this is required for transport activity, and the transporters also interact with many other membrane proteins that may control their cell-surface expression or other properties. 

Although there is structural homology among the transporters for 5-HT, norepinephrine and dopamine, some drugs exhibit great selectivity at inhibiting the activity of just one of these proteins. For example, the selective norepinephrine re-uptake inhibitor reboxetine is 150 times more potent at inhibiting norepinephrine transport... 

MAGUK membrane-associated guanylyl kinase homolog NET norepinephrine transporter... 

These eukaryotic glutamate transporters form a family that displays approx 50% overall identity and approx 60% overall similarity and is distinct from the GABA and norepinephrine transporter family. The eukaryotic glutamate transporters are also... 

Galli, A., Blakely, R. D., and DeFelice, L. J. (1996) Norepinephrine transporters have channel modes of conduction. Proc. Natl. Acad. Sci. USA 93, 8671-8676. 

Melikian, H. E., McDonald, J. K., Gu, H., Rudnick, G., Moore, K. R., and Blakely, R. D. (1994) Human norepinephrine transporter. Biosynthetic studies using a site-directed polyclonal antibody. J. Biol. Chem. 269,12290-12297. 

Brass, M., Hammermann, R., Brimijoin, S., and Bonisch, H. (1995) Antipeptide antibodies confirm the topology of the human norepinephrine transporter. J. Biol. Chem. 270,9197-9201. 

Giros, B., Wang, Y. M., Suter, S., McLeskey, S. B., Pifl, C., and Caron, M. G. (1994) Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. J. Biol. Chem. 269,15985-15988. 

Danek Burgess, K. S. and Justice, J. B., Jr. (1999) Effect of serine mutations in transmembrane domain 7 of the human norepinephrine transporter on substrate binding and transport. J. Neurochem. 73, 656-664. 

Paczkowski, F. A., Bonisch, H., and Bryan-Lluka, L. J. (2002) Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter. Pharmacogenetics 12,165-173. 

Monoamine reuptake inhibitors elevate extracellular levels of serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) in the brain by binding to one or more of the transporters responsible for reuptake, namely the serotonin transporter (SERT), the norepinephrine transporter (NET) and the dopamine transporter (DAT), thereby blocking the reuptake of the neurotransmitter(s) from the synaptic cleft [1], Monoamine reuptake inhibitors are an established drug class that has proven utility for the treatment of a number of CNS disorders, especially major depressive disorder (MDD). 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

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