[5] VMAT1 and VMAT2 were first identified in rats upon cloning cDNAs for proteins which gave non-amine accumulating recipient cells the ability to sequester monoamines.

[12] The first proton is thought to cause a change in VMAT1's conformation, which pushes a high affinity amine binding site, to which the monoamine attaches.

The second proton then causes a second change in the conformation which pulls the monoamine into the vesicle and greatly reduces the affinity of the binding site for amines.

[9] Several reuptake inhibitors of VMATs are known to exist, including reserpine (RES), tetrabenazine (TBZ), dihydrotetrabenazine (DTBZOH), and ketanserin (KET).

It is thought that RES exhibits competitive inhibition, binding to the same site as the monoamine substrate, as studies have shown that it can be displaced via introduction of norepinephrine.

Essentially, this means that certain compounds in the gut can be taken into these G cells and either amplify or inhibit the function of VMAT1, which will impact gastrin processing (conversion from G34 to G17).

[18][19] It is thought that disruption in transport of monoamine neurotransmitters due to variation in the VMAT1 gene may be relevant to the etiology of these mental disorders.

The study confirmed expression of VMAT1 in the brain at a protein and mRNA level, and found a significant difference between the two groups, suggesting that, at least for people of European descent, variation in the VMAT1 gene may confer susceptibility.

This study resulted in mostly inconclusive findings, but some indications that variation in the VMAT1 gene would confer susceptibility to schizophrenia in Japanese women.

[20] While these studies provide some promising insight into the cause of some of the most prevalent mental disorders, it is clear that additional research will be necessary in order to gain a full understanding.