Sodium-dependent norepinephrine transporter (NET) (NET)

The Sodium-dependent norepinephrine transporter (NET) is a monoamine transporter protein encoded by the SLC6A2 gene that mediates the reuptake of norepinephrine from the synaptic space (UniProt P23975). It plays a pivotal role in the termination of noradrenergic signaling in both the central nervous system and the sympathetic nervous system (NCBI Gene ID 6530). By controlling the concentration of norepinephrine, NET influences physiological states such as arousal, cognition, and cardiovascular homeostasis (StatPearls, Bupropion). Clinical evidence links NET dysfunction to several neuropsychiatric disorders, including major depressive disorder and attention-deficit/hyperactivity disorder (ADHD) (PubMed PMID: 10714171). Bupropion is a therapeutic agent that inhibits NET, alongside the dopamine transporter, to increase synaptic levels of these neurotransmitters (PubChem CID 444). This inhibition is utilized in the treatment of depression and as an aid for smoking cessation (StatPearls, Bupropion). However, because NET is also expressed in the periphery, its inhibition can lead to adverse effects like hypertension and tachycardia (PubMed PMID: 12750331). Understanding the structural and functional properties of NET is essential for developing selective inhibitors with improved safety profiles (PubMed PMID: 24814341).

Other names

SLC6A2Norepinephrine transporterNAT1NET1Solute carrier family 6 member 2

Inhibition of the reuptake of norepinephrine from the synaptic cleft into the presynaptic neuron, thereby increasing the concentration and duration of norepinephrine action at postsynaptic receptors.