Catecholamine transporters (DAT, NET)

Catecholamine transporters are essential membrane proteins that regulate the intensity and duration of catecholaminergic signaling by facilitating the reuptake of dopamine, norepinephrine, and epinephrine from the extracellular space [3, 11, 12]. The primary members of this group are the dopamine transporter (DAT; SLC6A3) and the norepinephrine transporter (NET; SLC6A2), which are sodium- and chloride-dependent symporters located on the plasma membranes of presynaptic neurons [10, 12]. By clearing neurotransmitters from the synaptic cleft, they prevent overstimulation of postsynaptic receptors and allow for the recycling of neurotransmitters into vesicular stores via the vesicular monoamine transporter (VMAT2) [3, 11]. Dysfunction of these transporters is linked to several major disorders, including Parkinson's disease, ADHD, depression, and substance use disorders [1, 2, 9, 11]. They are the primary targets for numerous pharmacological agents, including psychostimulants like methylphenidate and amphetamines, which increase synaptic catecholamine levels to treat cognitive and mood-related symptoms [11, 12]. Additionally, imaging of these transporters, particularly DAT, serves as a critical diagnostic tool for assessing the integrity of dopaminergic neurons in neurodegenerative conditions [1, 6]. These transporters also play a role in peripheral physiology, influencing cardiovascular tone and the stress response through the regulation of circulating catecholamines [1, 3, 5].

Other names

Monoamine transportersSLC6 family transportersUptake-1 transportersDopamine and norepinephrine transportersCatecholamine reuptake pumps

Inhibition of neurotransmitter reuptake from the synaptic cleft by blocking the transporter pore and, in the case of certain stimulants like amphetamines, induction of substrate-mediated neurotransmitter release through transport reversal [11, 12].