Norepinephrine_transporter

Norepinephrine transporter

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 and is encoded by the gene.

Certain antidepressant medications act to raise noradrenaline, such as the SNRIs 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, SNRIs would also raise dopamine levels in the synapse.

"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]

Genetics

The norepinephrine transporter is coded by a gene called "solute carrier family 6, member 2" with the gene symbol SLC6A2. In humans it is located on chromosome 16 locus 16q12.2. There are several variations in the gene, e.g., these single nucleotide polymorphism (SNP):

The Ala457Pro rare missense mutation results in a loss of function and has been associated with orthostatic intolerance (associated with postural orthostatic tachycardia syndrome) in one kindred. Orthostatic intolerance is, however, not typically associated with the mutation.

An epigenetic mechanism (hypermethylation of CpG islands in the NET gene promoter region) 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.

The SNPs rs3785143 and rs11568324 have been related to the attention-deficit hyperactivity disorder.

See also

References

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