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Dopamine transporter5/5/2023 On the other hand, the central roles have also presented these plasma membrane proteins as functional targets for drugs of abuse such as alcohol, cocaine, methamphetamine, and MDMA (3,4-methylenedioxymethamphetamine or Ecstasy). The extensive distribution of these transporters determines their central roles in neurotransmission and are ideal medication targets for a spectrum of monoamine-related neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), depression, anxiety, addiction, narcolepsy, fatigue, obesity, eating disorder, other mood disorders, schizophrenia (SCZ), bipolar disorder, and Parkinson's disease. 7 Importantly, these monoaminergic neurons intervene with each other and with many other types of neurons and innervate various brain regions including cortex, hippocampus, amygdale, and hypothalamus. VMAT1 is expressed transiently during brain development, and VMAT2 is the main vesicular transporter in these monoaminergic neurons. DAT is expressed in dopaminergic neurons that project mainly from the ventral tegmental area (VTA) and substantia nigra to prefrontal cortex, nucleus accumbens, and striatum SERT plays its role in the pons and upper brain stem NET is localized in the locus coeruleus and the lateral tegmental group that project into many other brain regions. 4–6īecause of the exclusive expression of each transporter in the corresponding neurons, these transporters are often used as markers of specific neurons. 3 Complete deletion of the VMAT2 gene causes developmental defect and embryonic lethality in mice. For instance, two loss-of-function DAT mutants, 元68Q and P395L, cause infantile parkinsonism-dystonia in humans. Loss of a transporter could cause severe disease or lethality. Therefore, the overall function of these four transporters is to regulate spatio-temporal components of monoamine transmission. In the membrane of intracellular synaptic vesicles is the vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), which use a proton gradient as the energy source to sequester cytosolic monoamines into the vesicles and then release the monoamines into the synaptic cleft by exocytosis. The major function of these transporters is to terminate monoamine transmission by inward transport of substrates away from the synaptic cleft. 1,2 These proteins use ion (Na +, Cl –) gradients as energy sources to move monoamines into or out of neurons. Monoamine transporters are transmembrane proteins located in plasma membranes of monoaminergic neurons, including the dopamine transporter (DAT), serotonin transporter (SERT, also expressed in platelets), and norepinephrine transporter (NET). Barak Caine, in Progress in Molecular Biology and Translational Science, 2011 I Introduction
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