Vesicular monoamine transporter 2

Solute carrier family 18 (vesicular monoamine transporter), member 2
Identifiers
Symbols	SLC18A2 ; SVAT; SVMT; VAT2; VMAT2
External IDs	OMIM: 193001 MGI: 106677 HomoloGene: 2298 IUPHAR: 1012 ChEMBL: 1893 GeneCards: SLC18A2 Gene
Gene ontology Molecular function • monoamine transmembrane transporter activity Cellular component • plasma membrane • integral component of plasma membrane • synaptic vesicle • membrane • clathrin-sculpted monoamine transport vesicle membrane Biological process • response to amphetamine • synaptic transmission • neurotransmitter secretion • locomotory behavior • response to toxic substance • post-embryonic development • monoamine transport • dopamine transport • death • sequestering of neurotransmitter • transmembrane transport • neurotransmitter loading into synaptic vesicle • negative regulation of reactive oxygen species biosynthetic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6571	214084
Ensembl	ENSG00000165646	ENSMUSG00000025094
UniProt	Q05940	Q8BRU6
RefSeq (mRNA)	NM_003054	NM_172523
RefSeq (protein)	NP_003045	NP_766111
Location (UCSC)	Chr 10: 117.24 – 117.28 Mb	Chr 19: 59.26 – 59.3 Mb
PubMed search	[1]	[2]

Distribution of VMAT2 in the human brain.

The vesicular monoamine transporter 2 (VMAT2) also known as solute carrier family 18 member 2 (SLC18A2) is a protein that in humans is encoded by the SLC18A2 gene. VMAT2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles. In nigrostriatal pathway and mesolimbic pathway dopamine-releasing neurons, VMAT2 function is also necessary for the vesicular release of the neurotransmitter GABA.

Binding sites and ligands

One binding site is that of dihydrotetrabenazine (DTBZ) and reserpine. Lobeline binds at this site. Amphetamine (TBZ site) and methamphetamine (reserpine site) bind at distinct sites to on VMAT2 to inhibit its function. Although the amphetamines inhibit VMAT2 presynaptically leading to diminished neurotransmitter, the primary mechanism for the enhancement of extracellular monoamines, like dopamine, is reversal of the dopamine transporter (DAT). Other VMAT2 inhibitors such as GZ-793A inhibit the reinforcing effects of methamphetamine, but without producing stimulant or reinforcing effects themselves.

Inhibition of VMAT2

VMAT2 is essential in the presynaptic neuron's ability to facilitate the release of neurotransmitters into the synaptic cleft. If VMAT2 function is inhibited or compromised, neurotransmitters, such as dopamine, cannot be released via normal transport (exocytosis, action potential) into the synapse. VMAT2 function inhibition can have many various effects on neurotransmitter function. Specifically of importance is its effect on the neurotransmitter dopamine.

Cocaine users display a marked reduction in VMAT2 immunoreactivity. Sufferers of cocaine-induced mood disorders displayed a significant loss of VMAT2 immunoreactivity; this might reflect damage to dopamine axon terminals in the striatum. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely addicted users.

External links

• Vesicular Monoamine Transporter 2 at the US National Library of Medicine Medical Subject Headings (MeSH)