vesicular monoamine transport proteins


Summary: A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.

Top Publications

  1. Saisho Y, Harris P, Butler A, Galasso R, Gurlo T, Rizza R, et al. Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas. J Mol Histol. 2008;39:543-51 pubmed publisher
    ..Although VMAT2 was not excluded as a target for beta cell mass measurement, expression of VMAT2 in PP cells predicts residual VMAT2 expression in human pancreas even in the absence of beta cells. ..
  2. Maurel A, Spreux Varoquaux O, Amenta F, Tayebati S, Tomassoni D, Seguelas M, et al. Vesicular monoamine transporter 1 mediates dopamine secretion in rat proximal tubular cells. Am J Physiol Renal Physiol. 2007;292:F1592-8 pubmed
    ..These data represent the first step toward the comprehension of the role of this transporter in renal dopamine handling and its involvement in pathological situations. ..
  3. Lin Z, Walther D, Yu X, Li S, Drgon T, Uhl G. SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism. Hum Mol Genet. 2005;14:1393-404 pubmed
    ..0038 by Fisher's exact tests). Therefore, SLC18A2 promoter haplotypes defined here create a foundation for transcriptional characterization of individuality and for association study on monoamine-related human diseases. ..
  4. Kawano M, Kawasaki A, Sakata Haga H, Fukui Y, Kawano H, Nogami H, et al. Particular subpopulations of midbrain and hypothalamic dopamine neurons express vesicular glutamate transporter 2 in the rat brain. J Comp Neurol. 2006;498:581-92 pubmed
    ..These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons. ..
  5. Lawal H, Chang H, Terrell A, Brooks E, Pulido D, Simon A, et al. The Drosophila vesicular monoamine transporter reduces pesticide-induced loss of dopaminergic neurons. Neurobiol Dis. 2010;40:102-12 pubmed publisher
    ..These results are the first to demonstrate an interaction between a VMAT and pesticides in vivo, and provide an important model to investigate the mechanisms by which pesticides and cellular DA may interact to kill dopaminergic cells. ..
  6. Bohnen N, Albin R, Koeppe R, Wernette K, Kilbourn M, Minoshima S, et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cereb Blood Flow Metab. 2006;26:1198-212 pubmed
    ..We conclude that (+)-[(11)C]DTBZ-PET imaging displays many properties necessary of a PD biomarker. ..
  7. Chang H, Grygoruk A, Brooks E, Ackerson L, Maidment N, Bainton R, et al. Overexpression of the Drosophila vesicular monoamine transporter increases motor activity and courtship but decreases the behavioral response to cocaine. Mol Psychiatry. 2006;11:99-113 pubmed
  8. Glatt C, Wahner A, White D, Ruiz Linares A, Ritz B. Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women. Hum Mol Genet. 2006;15:299-305 pubmed
    ..This finding is consistent with the prediction that increased sequestration of dopamine in secretory vesicles by VMAT2 is protective for PD. ..
  9. Noskova V, Bottalico B, Olsson H, Ehinger A, Pilka R, Casslén B, et al. Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2. Mol Hum Reprod. 2006;12:483-9 pubmed
    ..They can potentially influence the reproductive process by the uptake of extracellular histamine and subsequent release on demand. ..

More Information


  1. Boileau I, Rusjan P, Houle S, Wilkins D, Tong J, Selby P, et al. Increased vesicular monoamine transporter binding during early abstinence in human methamphetamine users: Is VMAT2 a stable dopamine neuron biomarker?. J Neurosci. 2008;28:9850-6 pubmed publisher
    ..If correct, (+)[(11)C]DTBZ might be a useful imaging probe to correlate changes in brain dopamine stores and behavior in users of methamphetamine. ..
  2. Guillot T, Richardson J, Wang M, Li Y, Taylor T, Ciliax B, et al. PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity. Neuropeptides. 2008;42:423-34 pubmed publisher
    ..The ability of PACAP38 to increase VMAT2 expression suggests that PACAP38 signaling pathways may constitute a novel therapeutic approach to treat and prevent disorders of dopamine storage. ..
  3. Lohoff F, Lautenschlager M, Mohr J, Ferraro T, Sander T, Gallinat J. Association between variation in the vesicular monoamine transporter 1 gene on chromosome 8p and anxiety-related personality traits. Neurosci Lett. 2008;434:41-5 pubmed publisher
    ..408, p=0.0004; STAI trait: Thr/Ile vs. Ile/Ile: T=3.074, p=0.009) but not in the male group. Our findings support the hypothesis that anxiety-related personality traits are associated with variation in the VMAT1/SLC18A1 gene. ..
  4. Mosharov E, Larsen K, Kanter E, Phillips K, Wilson K, Schmitz Y, et al. Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron. 2009;62:218-29 pubmed publisher
    ..Thus, an interaction between Ca2+, DA(cyt), and alpha-synuclein may underlie the susceptibility of SN neurons in PD, suggesting multiple therapeutic targets. ..
  5. Stephenson D, Childs M, Li Q, Carvajal Gonzalez S, Opsahl A, Tengowski M, et al. Differential loss of presynaptic dopaminergic markers in Parkinsonian monkeys. Cell Transplant. 2007;16:229-44 pubmed
    ..These findings have implications for the use of biomarkers of disease progression as well as for the assessment of neurorestorative strategies, such as cell replacement, for the treatment of PD. ..
  6. Goswami R, Ponde D, Kung M, Hou C, Kilbourn M, Kung H. Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol. 2006;33:685-94 pubmed
    ..Further studies are warranted to assess the utility of these (18)F-labeled DTBZ derivatives as PET tracers for the diagnosis of various neurodegenerative diseases. ..
  7. Taylor T, Caudle W, Shepherd K, Noorian A, Jackson C, Iuvone P, et al. Nonmotor symptoms of Parkinson's disease revealed in an animal model with reduced monoamine storage capacity. J Neurosci. 2009;29:8103-13 pubmed publisher
    ..Furthermore, monoamine dysfunction may contribute to many of the nonmotor symptoms of PD, and interventions aimed at restoring monoamine function may be beneficial in treating the disease...
  8. Tong J, Boileau I, Furukawa Y, Chang L, Wilson A, Houle S, et al. Distribution of vesicular monoamine transporter 2 protein in human brain: implications for brain imaging studies. J Cereb Blood Flow Metab. 2011;31:2065-75 pubmed publisher
  9. Tian L, Karimi M, Loftin S, Brown C, Xia H, Xu J, et al. No differential regulation of dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) binding in a primate model of Parkinson disease. PLoS ONE. 2012;7:e31439 pubmed publisher
    ..0005). These similar changes in DAT and VMAT2 binding sites in the striatal terminal fields of the surviving nigrostriatal neurons demonstrate that there is no differential regulation of these two sites at 2 months after MPTP infusion...
  10. Zhou Z, Kim J, Insolera R, Peng X, Fink D, Mata M. Rho GTPase regulation of ?-synuclein and VMAT2: implications for pathogenesis of Parkinson's disease. Mol Cell Neurosci. 2011;48:29-37 pubmed publisher
    ..The results suggest that RhoA signaling may be potential therapeutic target for the treatment of synucleinopathies. ..
  11. Schwab S, Franke P, Hoefgen B, Guttenthaler V, Lichtermann D, Trixler M, et al. Association of DNA polymorphisms in the synaptic vesicular amine transporter gene (SLC18A2) with alcohol and nicotine dependence. Neuropsychopharmacology. 2005;30:2263-8 pubmed
    ..0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence. ..
  12. Guillot T, Miller G. Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons. Mol Neurobiol. 2009;39:149-70 pubmed publisher
  13. Okamura N, Villemagne V, Drago J, Pejoska S, Dhamija R, Mulligan R, et al. In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133. J Nucl Med. 2010;51:223-8 pubmed publisher
    ..PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain...
  14. Raffo A, Hancock K, Polito T, Xie Y, Andan G, Witkowski P, et al. Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine. J Endocrinol. 2008;198:41-9 pubmed publisher
    ..Together, these data suggest that VMAT2 regulates in vivo glucose homeostasis and insulin production, most likely via its role in vesicular transport and storage of monoamines in beta-cells. ..
  15. Sager J, Torres G. Proteins interacting with monoamine transporters: current state and future challenges. Biochemistry. 2011;50:7295-310 pubmed publisher
  16. Freeby M, Goland R, Ichise M, Maffei A, Leibel R, Harris P. VMAT2 quantitation by PET as a biomarker for beta-cell mass in health and disease. Diabetes Obes Metab. 2008;10 Suppl 4:98-108 pubmed publisher
    ..Thus measurements of [(11)C] DTBZ in the pancreas provide an indirect measurement of BCM. Here we summarize our ongoing efforts to validate the clinical utility of this non-invasive approach to real-time BCM measurements. ..
  17. Tsao H, Lin K, Juang J, Skovronsky D, Yen T, Wey S, et al. Binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine (AV-133) to the vesicular monoamine transporter type 2 in rats. Nucl Med Biol. 2010;37:413-9 pubmed publisher
    ..In the present study, we examined the binding characteristics of 9-fluoropropyl-(+)-dihydrotetrabenzazine ([(18)F]AV-133), a potential PET tracer for BCM imaging, in rat pancreas and rat brain...
  18. Zhao C, Furnes M, Stenstrom B, Kulseng B, Chen D. Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study. Cell Tissue Res. 2008;331:575-87 pubmed
    ..Thus, obestatin and ghrelin co-localize with an anticipated monoamine in A-like cells in the stomach, and obestatin is found in pancreatic islets. ..
  19. Park S, Schulz E, Lee D. Disruption of dopamine homeostasis underlies selective neurodegeneration mediated by alpha-synuclein. Eur J Neurosci. 2007;26:3104-12 pubmed
    ..All of these results demonstrate that elevated cytoplasmic DA is a main factor underlying the early stage of alpha-Syn-mediated neurodegeneration. ..
  20. Essand M, Vikman S, Grawe J, Gedda L, Hellberg C, Oberg K, et al. Identification and characterization of a novel splicing variant of vesicular monoamine transporter 1. J Mol Endocrinol. 2005;35:489-501 pubmed
    ..Furthermore, while VMAT1 can take up serotonin, VMAT1Delta15 cannot, indicating different functions for the two forms of VMAT1...
  21. Colebrooke R, Humby T, Lynch P, McGowan D, Xia J, Emson P. Age-related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease. Eur J Neurosci. 2006;24:2622-30 pubmed
  22. Fagerholm V, Mikkola K, Ishizu T, Arponen E, Kauhanen S, Någren K, et al. Assessment of islet specificity of dihydrotetrabenazine radiotracer binding in rat pancreas and human pancreas. J Nucl Med. 2010;51:1439-46 pubmed publisher
  23. Partilla J, Dempsey A, Nagpal A, Blough B, Baumann M, Rothman R. Interaction of amphetamines and related compounds at the vesicular monoamine transporter. J Pharmacol Exp Ther. 2006;319:237-46 pubmed
    ..Finally, the VMAT(2) assays we have developed should prove useful for guiding the synthesis and evaluation of novel VMAT(2) agents as possible treatment agents for addictive disorders...
  24. Christiansen L, Tan Q, Iachina M, Bathum L, Kruse T, McGue M, et al. Candidate gene polymorphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population. Biol Psychiatry. 2007;61:223-30 pubmed
    ..007). These results suggest that variations in genes encoding the components of serotonin metabolism may influence the basic mood level and that different genetic factors may apply in men and women. ..
  25. Xiong N, Xiong J, Khare G, Chen C, Huang J, Zhao Y, et al. Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease. PLoS ONE. 2011;6:e20677 pubmed publisher
    ..Collectively, edaravone may provide novel clinical therapeutics for PD. ..
  26. Sun J, Xu J, Cairns N, Perlmutter J, Mach R. Dopamine D1, D2, D3 receptors, vesicular monoamine transporter type-2 (VMAT2) and dopamine transporter (DAT) densities in aged human brain. PLoS ONE. 2012;7:e49483 pubmed publisher
  27. Boger H, Mannangatti P, Samuvel D, Saylor A, Bender T, McGinty J, et al. Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging. Genes Brain Behav. 2011;10:186-98 pubmed publisher
    ..These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age. ..
  28. Lin K, Weng Y, Wey S, Hsiao I, Lu C, Skovronsky D, et al. Whole-body biodistribution and radiation dosimetry of 18F-FP-(+)-DTBZ (18F-AV-133): a novel vesicular monoamine transporter 2 imaging agent. J Nucl Med. 2010;51:1480-5 pubmed publisher
  29. Narendran R, Lopresti B, Martinez D, Mason N, Himes M, May M, et al. In vivo evidence for low striatal vesicular monoamine transporter 2 (VMAT2) availability in cocaine abusers. Am J Psychiatry. 2012;169:55-63 pubmed publisher
    ..Further research is necessary to understand the clinical relevance of this observation to relapse and outcome in abstinent cocaine abusers. ..
  30. Watabe M, Nakaki T. Mitochondrial complex I inhibitor rotenone inhibits and redistributes vesicular monoamine transporter 2 via nitration in human dopaminergic SH-SY5Y cells. Mol Pharmacol. 2008;74:933-40 pubmed publisher
  31. Caudle W, Colebrooke R, Emson P, Miller G. Altered vesicular dopamine storage in Parkinson's disease: a premature demise. Trends Neurosci. 2008;31:303-8 pubmed publisher
    ..This review seeks to revisit the pathogenicity of cytosolic dopamine and further address the critical role of neurotransmitter storage in dopamine-mediated neurotoxicity. ..
  32. Greer C, Grygoruk A, Patton D, Ley B, Romero Calderon R, Chang H, et al. A splice variant of the Drosophila vesicular monoamine transporter contains a conserved trafficking domain and functions in the storage of dopamine, serotonin, and octopamine. J Neurobiol. 2005;64:239-58 pubmed
    ..Our data suggest that DVMAT-A functions as a vesicular transporter for DA, 5HT, and octopamine in vivo, and will provide a powerful invertebrate model for the study of transporter trafficking and regulation. ..
  33. Caudle W, Richardson J, Wang M, Taylor T, Guillot T, McCormack A, et al. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci. 2007;27:8138-48 pubmed
    ..In addition, the altered dopamine homeostasis resulting from reduced VMAT2 function may be conducive to pathogenic mechanisms induced by genetic or environmental factors thought to be involved in Parkinson's disease. ..
  34. Crowley J, Lipsky R, Lucki I, Berrettini W. Variation in the genes encoding vesicular monoamine transporter 2 and beta-1 adrenergic receptor and antidepressant treatment outcome. Psychiatr Genet. 2008;18:248-51 pubmed publisher
    ..These data do not rule out the possible involvement of SLC18A2 or ADRB1 in antidepressant treatment response as these genes may contribute a small effect size or interact epistatically with other genes. ..
  35. Li H, Waites C, Staal R, Dobryy Y, Park J, Sulzer D, et al. Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines. Neuron. 2005;48:619-33 pubmed
    ..VMAT2 thus defines a population of secretory vesicles that mediate the activity-dependent somatodendritic release of multiple retrograde signals involved in synaptic function, growth, and plasticity. ..
  36. Anlauf M, Schafer M, Schwark T, von Wurmb Schwark N, Brand V, Sipos B, et al. Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis. J Histochem Cytochem. 2006;54:201-13 pubmed
  37. Sala G, Brighina L, Saracchi E, Fermi S, Riva C, Carrozza V, et al. Vesicular monoamine transporter 2 mRNA levels are reduced in platelets from patients with Parkinson's disease. J Neural Transm (Vienna). 2010;117:1093-8 pubmed publisher
  38. Tsao H, Skovronsky D, Lin K, Yen T, Wey S, Kung M. Sigma receptor binding of tetrabenazine series tracers targeting VMAT2 in rat pancreas. Nucl Med Biol. 2011;38:1029-34 pubmed publisher
    ..Identification of the cause of background binding of [(18)F]AV-133 to rat pancreatic tissue may lead to improved methods for quantification. ..
  39. Kariya S, Hirano M, Takahashi N, Furiya Y, Ueno S. Lack of association between polymorphic microsatellites of the VMAT2 gene and Parkinson's disease in Japan. J Neurol Sci. 2005;232:91-4 pubmed
    ..Our data suggest that the polymorphic region of the VMAT2 gene studied here is not closely related to PD. ..
  40. Chen C, Huang S, Zhang L, Liu Y. Synaptophysin enhances the neuroprotection of VMAT2 in MPP+-induced toxicity in MN9D cells. Neurobiol Dis. 2005;19:419-26 pubmed
    ..Our work indicates that both the expression level of VMAT2 and capacity of vesicular packaging of DA are important in protecting DAergic cells from MPP+ toxicity. ..
  41. Lin Z, Zhao Y, Chung C, Zhou Y, Xiong N, Glatt C, et al. High regulatability favors genetic selection in SLC18A2, a vesicular monoamine transporter essential for life. FASEB J. 2010;24:2191-200 pubmed publisher
    ..These findings suggest that greater diversity of transcriptional regulations is the driving force for the haplotype selection in SLC18A2. ..
  42. Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, et al. Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest. 2006;116:1506-13 pubmed
    ..These studies suggest that PET-based quantitation of VMAT2 receptors provides a noninvasive measurement of BCM that could be used to study the pathogenesis of diabetes and to monitor therapeutic interventions. ..
  43. Goland R, Freeby M, PARSEY R, Saisho Y, Kumar D, Simpson N, et al. 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009;50:382-9 pubmed publisher
  44. Mason S, Baker K, Davis K, Pogorelov V, Malbari M, Ritter R, et al. Differential sensitivity to SSRI and tricyclic antidepressants in juvenile and adult mice of three strains. Eur J Pharmacol. 2009;602:306-15 pubmed publisher
    ..Further examination of these effects is needed to determine whether it may be related to age-dependent difference in the clinical response to antidepressants of these classes. ..
  45. Chen M, Kuwabara H, Zhou Y, Adams R, Brasic J, McGlothan J, et al. VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. J Neurochem. 2008;105:78-90 pubmed
    ..Genetic or environmental factors that decrease VMAT2 function may be important determinants of PD...
  46. Maffei A, Liu Z, Witkowski P, Moschella F, Del Pozzo G, Liu E, et al. Identification of tissue-restricted transcripts in human islets. Endocrinology. 2004;145:4513-21 pubmed
    ..We report here the first comparison of gene expression profiles of human islets with other tissues and the identification of a target molecule with possible use in determining islet cell masses. ..
  47. Truong J, Rau K, Hanson G, Fleckenstein A. Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration. Eur J Pharmacol. 2003;474:223-6 pubmed
    ..The implications of this finding relevant to the treatment of neurodegenerative disorders are discussed. ..
  48. Anlauf M, Eissele R, Schafer M, Eiden L, Arnold R, Pauser U, et al. Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. J Histochem Cytochem. 2003;51:1027-40 pubmed
    ..Monoamine storage mediated by VMAT1 in EC cells is apparently maintained in EC cell tumors. In contrast, many insulinomas appear to lose their ability to accumulate monoamines via VMAT2. ..
  49. Little K, Krolewski D, Zhang L, Cassin B. Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users. Am J Psychiatry. 2003;160:47-55 pubmed
    ..Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely dependent patients. ..
  50. Sandoval V, Riddle E, Hanson G, Fleckenstein A. Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors. J Neurosci. 2002;22:8705-10 pubmed
    ..These observations suggest a role for DA in the MPD-induced redistribution of VMAT-2. The implications of this phenomenon will be discussed. ..
  51. Pothos E. Regulation of dopamine quantal size in midbrain and hippocampal neurons. Behav Brain Res. 2002;130:203-7 pubmed
    ..We suggest that plasticity in dopamine quantal seems likely to be involved in both normal synaptic modification and disease states. ..
  52. Kilbourn M, Kuszpit K, Sherman P. Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice. Synapse. 2000;35:250-5 pubmed
    ..These studies indicate that the losses of the neuronal membrane and vesicular transporters are not always equal, and do not occur in the same time frame, after administration of the neurotoxin MPTP. ..
  53. Henry J, Sagne C, Bedet C, Gasnier B. The vesicular monoamine transporter: from chromaffin granule to brain. Neurochem Int. 1998;32:227-46 pubmed
    ..The possibility of regulations at the vesicular transporter level and of their effect on the quantum size has to be investigated. The vesicular monoamine transporter is also an important target for brain imaging. ..