Vesicular monoamine transporter 2

Vesicular monoamine transporter 2 (VMAT2) 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.

Function

VMAT2 is found primarily in the membrane of synaptic vesicles in neuronal cells. It acts to transport monoamines, including neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine, from the cytosol into these vesicles. This transport is against a concentration gradient and is facilitated by the proton gradient across the vesicle membrane.

Clinical significance

Alterations in the function of VMAT2 are implicated in various neurological disorders, including Parkinson's disease, schizophrenia, and depression. In Parkinson's disease, a decrease in VMAT2 function may result in less sequestration of dopamine in vesicles, leading to the neurotoxicity that characterizes this condition. In schizophrenia and depression, alterations in monoamine transmission are thought to be involved, and changes in VMAT2 function may play a role in these conditions.

Pharmacology

Several drugs act at VMAT2 to influence its function. These include reserpine, a drug that inhibits VMAT2 and has been used in the treatment of hypertension and psychosis, and tetrabenazine, which also inhibits VMAT2 and is used in the treatment of Huntington's disease. In addition, amphetamine and methamphetamine are thought to act in part by causing a reversal of VMAT2 function, leading to an increase in the release of monoamines into the synapse.

See also

• Vesicular monoamine transporter 1
• Monoamine neurotransmitter
• Synaptic vesicle