Sodium-dependent norepinephrine transporter (NET)

The Norepinephrine transporter (NET), also known as SLC6A2, is a multi-pass membrane protein belonging to the sodium:neurotransmitter symporter family. Encoded by the SLC6A2 gene, it has 617 amino acids and 12 membrane-spanning domains. Its primary function is the sodium- and chloride-dependent reuptake of norepinephrine from the synaptic cleft into presynaptic terminals, terminating neurotransmission and regulating noradrenergic signaling. NET also transports dopamine. It is a crucial therapeutic target for drugs like antidepressants and psychostimulants, which block its reuptake activity to increase synaptic norepinephrine levels. NET function is implicated in neuropsychiatric disorders, including ADHD, and cardiovascular conditions like orthostatic intolerance. Furthermore, NET expression in neuroendocrine tumors makes it a target for imaging and targeted therapy using agents like MIBG. Inhibition of NET can affect blood pressure and heart rate.

Other names

Noradrenaline transporter (NAT)Solute carrier family 6 member 2NAT1NET1

Drugs targeting NET typically block the reuptake of norepinephrine, increasing its concentration in the synaptic cleft. Some drugs like MIBG are transported by NET into cells, making it useful for imaging and targeted therapy of neuroendocrine tumors.