Norepinephrine transporter

The noradrenaline transporter or 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."

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.

A loss of function mutation in the noradrenaline transporter has been associated with postural orthostatic tachycardia syndrome in one kindred. 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 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]"