The vesicular amine transporters (VATs) are putative 12 TM domain proteins that function to transport singly positively charged amine neurotransmitters and hormones from the cytoplasm and concentrate them within secretory vesicles. They function as amine/proton antiporters driven by secondary active transport utilizing the proton gradient established by a multi-subunit vacuolar ATPase that acidifies secretory vesicles (reviewed by [4]). The vesicular acetylcholine transporter (VAChT; [8]) localizes to cholinergic neurons, but non-neuronal expression has also been claimed [12]. Vesicular monoamine transporter 1 (VMAT1, [6]) is mainly expressed in peripheral neuroendocrine cells, but most likely not in the CNS, whereas VMAT2 [7] distributes between both central and peripheral sympathetic monoaminergic neurones [5]. The vescular polyamine transporter (VPAT) is highly expressed in the lungs and placenta, with moderate expression in brain and testis, and with low expression in heart and skeletal muscle [9]. VPAT mediates vesicular accumulation of polyamines in mast cells [14].

pK_i values for endogenous and synthetic substrate inhibitors of human VMAT1 and VMAT2 are for inhibition of [³H]5-HT uptake in transfected and permeabilised CV-1 cells as detailed by [7]. In addition to the monoamines listed in the table, the trace amines tyramine and β-phenylethylamine are probable substrates for VMAT2 [5]. Probes listed in the table are those currently employed; additional agents have been synthesized (e.g. [16]).

* Key recommended reading is highlighted with an asterisk

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Chaudhry FA, Edwards RH, Fonnum F. (2008) Vesicular neurotransmitter transporters as targets for endogenous and exogenous toxic substances. Annu Rev Pharmacol Toxicol, 48: 277-301. [PMID:17883368]

Eiden LE, Schäfer MK, Weihe E, Schütz B. (2004) The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine. Pflugers Arch, 447 (5): 636-40. [PMID:12827358]

Eiden LE, Weihe E. (2011) VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse. Ann N Y Acad Sci, 1216: 86-98. [PMID:21272013]

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Fleckenstein AE, Volz TJ, Hanson GR. (2009) Psychostimulant-induced alterations in vesicular monoamine transporter-2 function: neurotoxic and therapeutic implications. Neuropharmacology, 56 Suppl 1: 133-8. [PMID:18662707]

Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR. (2007) New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol, 47: 681-98. [PMID:17209801]

* German CL, Baladi MG, McFadden LM, Hanson GR, Fleckenstein AE. (2015) Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease. Pharmacol Rev, 67 (4): 1005-24. [PMID:26408528]

Giboureau N, Som IM, Boucher-Arnold A, Guilloteau D, Kassiou M. (2010) PET radioligands for the vesicular acetylcholine transporter (VAChT). Curr Top Med Chem, 10 (15): 1569-83. [PMID:20583990]

Guillot TS, Miller GW. (2009) Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Mol Neurobiol, 39 (2): 149-70. [PMID:19259829]

Khare P, White AR, Mulakaluri A, Parsons SM. (2010) Equilibrium binding and transport by vesicular acetylcholine transporter. Methods Mol Biol, 637: 181-219. [PMID:20419436]

* Lohr KM, Masoud ST, Salahpour A, Miller GW. (2017) Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease. Eur J Neurosci, 45 (1): 20-33. [PMID:27520881]

* Omote H, Miyaji T, Hiasa M, Juge N, Moriyama Y. (2016) Structure, Function, and Drug Interactions of Neurotransmitter Transporters in the Postgenomic Era. Annu Rev Pharmacol Toxicol, 56: 385-402. [PMID:26514205]

Parsons SM. (2000) Transport mechanisms in acetylcholine and monoamine storage. FASEB J, 14 (15): 2423-34. [PMID:11099460]

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Ramamoorthy S, Shippenberg TS, Jayanthi LD. (2011) Regulation of monoamine transporters: Role of transporter phosphorylation. Pharmacol Ther, 129 (2): 220-38. [PMID:20951731]

Schuldiner S, Shirvan A, Linial M. (1995) Vesicular neurotransmitter transporters: from bacteria to humans. Physiol Rev, 75 (2): 369-92. [PMID:7724667]

* Sitte HH, Freissmuth M. (2015) Amphetamines, new psychoactive drugs and the monoamine transporter cycle. Trends Pharmacol Sci, 36 (1): 41-50. [PMID:25542076]

Van der Kloot W. (2003) Loading and recycling of synaptic vesicles in the Torpedo electric organ and the vertebrate neuromuscular junction. Prog Neurobiol, 71 (4): 269-303. [PMID:14698765]

* Wimalasena K. (2011) Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry. Med Res Rev, 31 (4): 483-519. [PMID:20135628]

Zheng G, Dwoskin LP, Crooks PA. (2006) Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS J, 8 (4): E682-92. [PMID:17233532]

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2. Bravo DT, Kolmakova NG, Parsons SM. (2005) New transport assay demonstrates vesicular acetylcholine transporter has many alternative substrates. Neurochem Int, 47 (4): 243-7. [PMID:15979764]

3. Efange SM, Mach RH, Smith CR, Khare AB, Foulon C, Akella SK, Childers SR, Parsons SM. (1995) Vesamicol analogues as sigma ligands. Molecular determinants of selectivity at the vesamicol receptor. Biochem Pharmacol, 49 (6): 791-7. [PMID:7702637]

4. Eiden LE, Schäfer MK, Weihe E, Schütz B. (2004) The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine. Pflugers Arch, 447 (5): 636-40. [PMID:12827358]

5. Eiden LE, Weihe E. (2011) VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse. Ann N Y Acad Sci, 1216: 86-98. [PMID:21272013]

6. Erickson JD, Eiden LE. (1993) Functional identification and molecular cloning of a human brain vesicle monoamine transporter. J Neurochem, 61 (6): 2314-7. [PMID:8245983]

7. Erickson JD, Schafer MK, Bonner TI, Eiden LE, Weihe E. (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci USA, 93 (10): 5166-71. [PMID:8643547]

8. Erickson JD, Varoqui H, Schäfer MK, Modi W, Diebler MF, Weihe E, Rand J, Eiden LE, Bonner TI, Usdin TB. (1994) Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus. J Biol Chem, 269 (35): 21929-32. [PMID:8071310]

9. Hiasa M, Miyaji T, Haruna Y, Takeuchi T, Harada Y, Moriyama S, Yamamoto A, Omote H, Moriyama Y. (2014) Identification of a mammalian vesicular polyamine transporter. Sci Rep, 4: 6836. [PMID:25355561]

10. Khare P, Ojeda AM, Chandrasekaran A, Parsons SM. (2010) Possible important pair of acidic residues in vesicular acetylcholine transporter. Biochemistry, 49 (14): 3049-59. [PMID:20225888]

11. Kung MP, Canney DJ, Frederick D, Zhuang Z, Billings JJ, Kung HF. (1994) Binding of 125I-iodovinyltetrabenazine to CNS vesicular monoamine transport sites. Synapse, 18 (3): 225-32. [PMID:7855735]

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13. Sievert MK, Ruoho AE. (1997) Peptide mapping of the [125I]Iodoazidoketanserin and [125I]2-N-[(3'-iodo-4'-azidophenyl)propionyl]tetrabenazine binding sites for the synaptic vesicle monoamine transporter. J Biol Chem, 272 (41): 26049-55. [PMID:9325342]

14. Takeuchi T, Harada Y, Moriyama S, Furuta K, Tanaka S, Miyaji T, Omote H, Moriyama Y, Hiasa M. (2017) Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells. J Biol Chem, 292 (9): 3909-3918. [PMID:28082679]

15. Varoqui H, Erickson JD. (1996) Active transport of acetylcholine by the human vesicular acetylcholine transporter. J Biol Chem, 271 (44): 27229-32. [PMID:8910293]

16. Zhu L, Liu J, Kung HF. (2009) Synthesis and evaluation of 2-amino-dihydrotetrabenzine derivatives as probes for imaging vesicular monoamine transporter-2. Bioorg Med Chem Lett, 19 (17): 5026-8. [PMID:19632829]