Dopamine transporter (DAT) and Norepinephrine transporter (NET) (DAT, NET)

The dopamine transporter (DAT) and norepinephrine transporter (NET) are closely related members of the sodium- and chloride-dependent neurotransmitter: sodium symporter family (SLC6). DAT is primarily responsible for reuptake of dopamine from the synaptic cleft, thereby terminating dopaminergic signaling and regulating extracellular dopamine concentrations[3][5][6]. NET is involved in the reuptake of norepinephrine (noradrenaline), and to some degree dopamine, from both the central and peripheral nervous system[5][1][4]. Each transporter consists of 12 transmembrane domains and functions via coupling neurotransmitter reuptake with sodium and chloride ion gradients. Inhibition of these transporters by various drugs increases synaptic monoamine levels, underlying the therapeutic effects of antidepressants, psychostimulants, and drugs used to treat chronic pain and ADHD[3][4][5][6][2]. Alterations in transporter function contribute to the pathogenesis of mood disorders, ADHD, neurodegeneration, chronic pain, and risk of substance abuse[5].

Other names

DAT (dopamine transporter)NET (norepinephrine transporter)SLC6A2 (NET gene symbol)SLC6A3 (DAT gene symbol)Noradrenaline transporterMonoamine transporter

Inhibition of neurotransmitter reuptake (competitive or non-competitive inhibition of transporter function) Competitive binding at central substrate site (e.g., cocaine, antidepressants) Indirect increase in synaptic neurotransmitter concentration Some drugs act as substrate analogues to induce transporter-mediated efflux (reverse transport, e.g., amphetamines)