Vesicular monoamine transporter

The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membrane of synaptic vesicles of presynaptic neurons. It acts to transport monoamine neurotransmitters – such as dopamine, serotonin, norepinephrine, epinephrine, and histamine – into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import.

Pharmaceutical drugs that target VMATs have possible applications for many conditions, leading to a plethora of biological research. These applications include hypertension, drug addiction, psychiatric disorders, Parkinson's disease, and other neurological disorders. Many drugs that target VMAT act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing.

The two VMAT isoforms are:

Monoamines transported by VMATs are mainly noradrenaline, adrenaline, dopamine, serotonin, histamine, and trace amines. Exogenous substrates include guanethidine and MPP+.

VMAT research began in 1958 with the discovery of secretory vesicles by Nils-Åke Hillarp. VMATs have been studied for nearly four decades. In the 1970s, scientists such as Arvid Carlsson recognized the need to understand how transport systems and ion gradients work in different organisms in order to explore new treatment options such as Reserpine. Researchers discovered inhibitors that blocked the uptake of neurotransmitters into vesicles, suggesting the existence of VMATs. A decade later molecular genetic tools have improved methods for protein identification. Scientists have used these tools to analyze DNA and amino acid sequences, discovering that transporters in bacteria and humans were very similar. This finding illustrated the importance and universality of transporters. The transporters were first structurally identified by cloning VMATs in rats. VMAT was first isolated and purified in bovine chromaffin granules, in both native and denatured forms.

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