Sodium-dependent noradrenaline transporter (NET) (NET)

The Sodium-dependent noradrenaline transporter (NET), also known as the norepinephrine transporter, is a transmembrane protein encoded by the SLC6A2 gene that belongs to the solute carrier family 6 [2, 3]. It is primarily responsible for the high-affinity reuptake of norepinephrine from the synaptic cleft into presynaptic neurons, a process historically referred to as "Uptake 1" [14]. By clearing norepinephrine, NET terminates its physiological action and maintains neurotransmitter homeostasis in both the central and peripheral nervous systems [1, 9]. This regulation is vital for modulating mood, arousal, cognition, and autonomic functions such as blood pressure and heart rate [1, 8]. Dysregulation of NET is implicated in several neuropsychiatric and cardiovascular disorders, including major depressive disorder, attention-deficit hyperactivity disorder (ADHD), and postural orthostatic tachycardia syndrome (POTS) [5, 7, 13]. Consequently, NET is a major therapeutic target for antidepressants, such as selective norepinephrine reuptake inhibitors (NRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), as well as psychostimulants used to treat ADHD [6, 20]. These drugs typically act by inhibiting the transporter, thereby increasing the availability of norepinephrine in the synapse to enhance adrenergic signaling [9, 21].

Other names

Norepinephrine transporterSLC6A2NAT1NET1Solute carrier family 6 member 2Noradrenaline transporterUptake 1 transporter

Inhibition of norepinephrine reuptake from the synaptic cleft into presynaptic neurons; substrate-mediated reverse transport (release) of norepinephrine.