Norepinephrine reuptake transporter (NET)

The Norepinephrine reuptake transporter (NET) is a monoamine transporter responsible for the sodium-chloride (Na+/Cl−)-dependent reuptake of extracellular norepinephrine (NE) from the synapse into presynaptic neurons. It is encoded by the SLC6A2 gene and consists of 12 transmembrane domains. NET regulates the concentration of NE in the synaptic cleft, with as much as 90% of released NE being taken back up. It functions by coupling the influx of Na+ and Cl− ions with NE transport at a 1:1:1 ratio. NET also transports dopamine and is involved in controlling mood, arousal, memory, learning, and pain perception. Its function and cell surface expression are dynamically regulated, notably by phosphorylation. Dysregulation of NET is associated with various neuropsychiatric diseases, and genetic variations have been implicated in conditions like Postural orthostatic tachycardia syndrome and panic disorder. NET is a therapeutic target for numerous drugs, including antidepressants, psychostimulants, and ADHD medications. Blockage of NET is useful in treating various CNS disorders like ADHD, panic disorders, suicidal disorders, and depression, and may play a role in preventing SUDEP. Drugs interacting with NET include sNRIs like atomoxetine, maprotiline, reboxetine, and viloxazine, as well as triple reuptake inhibitors.

Other names

Norepinephrine transporter

Inhibition of norepinephrine reuptake from the synaptic cleft