Vesicular monoamine transporter (VMAT) (VMAT)

Vesicular monoamine transporters (VMATs) are integral membrane proteins that belong to the solute carrier family 18 (SLC18) and are responsible for the packaging of monoamine neurotransmitters into synaptic vesicles. They utilize a proton gradient generated by V-type ATPases to transport dopamine, serotonin, norepinephrine, epinephrine, and histamine from the neuronal cytosol into storage vesicles for subsequent exocytotic release [4, 8]. There are two primary isoforms: VMAT1 (SLC18A1), which is predominantly expressed in peripheral neuroendocrine cells, and VMAT2 (SLC18A2), which is the major isoform in the central nervous system [5, 11]. VMATs play a critical role in regulating the intensity of neurotransmission and protecting neurons from the toxic effects of cytosolic monoamine accumulation and oxidative stress [13, 17]. Clinically, VMAT2 is a significant therapeutic target for hyperkinetic movement disorders, such as Huntington's disease-related chorea and tardive dyskinesia, where inhibitors like tetrabenazine, deutetrabenazine, and valbenazine are used to deplete synaptic dopamine [2, 9]. Beyond movement disorders, VMAT2 density is utilized as a biomarker in neuroimaging to assess dopaminergic integrity in Parkinson's disease and to estimate pancreatic beta-cell mass in diabetes research [7, 16].

Other names

VMAT1VMAT2SLC18A1SLC18A2Solute carrier family 18 member 1Solute carrier family 18 member 2Chromaffin granule amine transporterBrain-specific vesicular monoamine transporterVesicular monoamine transporter 1Vesicular monoamine transporter 2

Inhibition of VMAT (primarily VMAT2) prevents the uptake of monoamine neurotransmitters (dopamine, serotonin, norepinephrine) into synaptic vesicles, leading to their depletion and reduced synaptic release [2, 6, 10].