Is VMAT2 an antiporter?

As a 12-transmembrane H+-ATPase antiporter, VMAT2 is evolutionarily related to a family of toxin extruding antiporters, which explains its ability to also sequester neuronal toxicants from the cytosol into vesicles.

What is VMAT pharmacology?

Vesicular monoamine transporters (VMAT) are responsible for the uptake of cytosolic monoamines into synaptic vesicles in monoaminergic neurons. Two closely related VMATs with distinct pharmacological properties and tissue distributions have been characterized.

Where are VMAT2 pumps located?

VMAT2 is expressed in all monoaminergic neurons of the brain, including those expressing dopamine (DA), serotonin (5-HT), norepinephrine (NE), epinephrine (EPI), and histamine (HIS).

What does VMAT inhibitor do?

The vesicular monoamine transporter type 2 (VMAT2) inhibitors are agents that cause a depletion of neuroactive peptides such as dopamine in nerve terminals and are used to treat chorea due to neurodegenerative diseases (such as Huntington chorea) or dyskinesias due to neuroleptic medications (tardive dyskinesia).

What is a VMAT2 inhibitor?

Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States.

What is VMAT2 receptor?

VMAT2 is an integral membrane protein that transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine—from cellular cytosol into synaptic vesicles.

What do VMAT inhibitors do?

What neurotransmitters are monoamines?

Monoamine neurotransmitters include serotonin and the catecholamines dopamine, adrenaline, and noradrenaline. These compounds have multiple functions including modulation of psychomotor function, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, hormone secretion, body temperature, and pain.

What is VMAT dopamine?

The vesicular monoamine transporter (VMAT) is a membrane-embedded protein that transports monoamine neurotransmitter molecules into intraneuronal storage vesicles to allow subsequent release into the synapse.

What type of transporter is VMAT?

The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons.

How do VMAT2 inhibitors work?

Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disor … The basal ganglia and dopaminergic pathways play a central role in hyperkinetic movement disorders.

How does VMAT2 protect β-cells from the toxic effects of oxidative stress?

Here, we found that VMAT2 acts to protect β-cells from the toxic effects of oxidative stress triggered by excessive insulin secretion through the compartmentalization of dopamine, which prevents its degradation.

Does VMAT2 deletion increase ROS production?

The reduction in dopamine content was attributed to the MAO-mediated cytoplasmic degradation of dopamine, which contributes to ROS production through H2O2synthesis during substrate degradation (30). We hypothesized that ROS production in the islets of βVmat2KO mice is higher, as VMAT2 depletion leads to increased cytoplasmic dopamine.

What is the function of VMAT2 in pancreatic β cells?

In the context of high demand for insulin secretion, the absence of VMAT2 leads to elevated ROS in β-cells, which accelerates β-cell dedifferentiation and β-cell loss. Therefore, VMAT2 controls the amount of dopamine in β-cells, thereby protecting pancreatic β-cells from excessive oxidative stress.