Norepinephrine transporter (NET) and Serotonin transporter (SERT) (NET/SERT)

The Norepinephrine transporter (NET) and Serotonin transporter (SERT) are sodium-dependent symporters that play a pivotal role in terminating the action of monoamine neurotransmitters within the synaptic cleft (UniProt P23975, P31645). NET is responsible for the reuptake of norepinephrine, while SERT facilitates the reuptake of serotonin into the presynaptic neuron, thereby regulating the concentration and duration of signaling for these molecules (NIH, StatPearls). These transporters are essential for modulating mood, arousal, cognition, and pain perception. Dysfunctional transport or altered expression of NET and SERT are implicated in various psychiatric disorders, including major depressive disorder, generalized anxiety disorder, and attention-deficit/hyperactivity disorder (ADHD) (PubMed). Therapeutic intervention often involves serotonin-norepinephrine reuptake inhibitors (SNRIs), which bind to both transporters to increase the extracellular levels of serotonin and norepinephrine, enhancing neurotransmission (StatPearls). While effective for depression and chronic pain, dual inhibition can cause side effects such as hypertension, tachycardia, and sexual dysfunction due to the systemic increase in monoamine activity (PubChem).

Other names

Sodium-dependent noradrenaline transporterSodium-dependent serotonin transporterSLC6A2SLC6A4Solute carrier family 6 member 2Solute carrier family 6 member 4NETSERT5-HTTNAT1

Inhibition of the reuptake of serotonin and norepinephrine from the synaptic cleft into the presynaptic neuron, increasing their extracellular concentrations and enhancing postsynaptic signaling (StatPearls).