The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membranes of synaptic vesicles of presynaptic neurons. It transports 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, including hypertension, drug addiction, psychiatric disorders, Parkinson's disease, and other neurological disorders. Many drugs that target VMATs act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing. Monoamines Monoamines transported by VMATs are mainly noradrenaline, adrenaline, dopamine, serotonin, histamine, and trace amines. Exogenous substrates include guanethidine and MPP+. Discovery VMAT research began in 1958 when Nils-Åke Hillarp discovered secretory vesicles. In the 1970s, scientists like 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 (RES). 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, and discovered that transporters in bacteria and humans were very similar, which emphasized the importance and universality of transporters. The transporters were first structurally identified by cloning VMATs in rats. The VMAT were first isolated and purified in bovine chromaffin granules, in both its native and denatured forms. Location There are two types of VMATs expressed in humans: VMAT1 and VMAT2. VMAT1 is expressed mainly in large dense-core vesicles (LDCVs) of the peripheral nervous system. VMAT1 may be found in neuroendocrine cells, particularly chromaffin and enterochromaffin granules, which are primarily found in the medulla of the adrenal glands. VMAT2 favors expression in a variety of monoaminergic cells of the central nervous system, such as the brain, sympathetic nervous system, mast cells, It is prevalent in β-cells, expressed in blood platelets, and co-expressed in chromaffin cells. Expression of the two transporters in internal organs seems to differ between species: only VMAT1 is expressed in rat adrenal medulla cells, whereas VMAT2 is the major transporter in bovine adrenal medulla cells. Structure and function VMAT1