vesicular biogenic amine transport proteins


Summary: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.

Top Publications

  1. Erickson J, Eiden L. Functional identification and molecular cloning of a human brain vesicle monoamine transporter. J Neurochem. 1993;61:2314-7 pubmed
    ..The virtually identical transport characteristics of rvMAT1 and hvMAT1 confirm the relevance of neuropharmacological studies of rat brain biogenic amine uptake and storage to human brain neurochemistry. ..
  2. Mooslehner K, Chan P, Xu W, Liu L, Smadja C, Humby T, et al. Mice with very low expression of the vesicular monoamine transporter 2 gene survive into adulthood: potential mouse model for parkinsonism. Mol Cell Biol. 2001;21:5321-31 pubmed
    ..They may also, however, be of use in probing other aspects of monoaminergic function and dysfunction in the brain, the latter making important contributions to the pathogenesis of schizophrenia and addiction. ..
  3. Kolby L, Bernhardt P, Ahlman H, Wangberg B, Johanson V, Wigander A, et al. A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake. Am J Pathol. 2001;158:745-55 pubmed
    ..This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms. ..
  4. Augood S, Hollingsworth Z, Albers D, Yang L, Leung J, Breakefield X, et al. Dopamine transmission in DYT1 dystonia. Adv Neurol. 2004;94:53-60 pubmed
  5. Ekue A, Boulanger J, Morissette M, Di Paolo T. Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice. J Neuroendocrinol. 2002;14:731-6 pubmed
    ..In addition, 17beta-oestradiol completely prevented the MPTP-induced decrease of DAT mRNA, whereas androgens did not. The present results show that androgens are unable to protect against MPTP-induced dopaminergic toxicity. ..
  6. Cordeiro M, Gundersen C, Umbach J. Lithium ions modulate the expression of VMAT2 in rat brain. Brain Res. 2002;953:189-94 pubmed
  7. Duerr J, Gaskin J, Rand J. Identified neurons in C. elegans coexpress vesicular transporters for acetylcholine and monoamines. Am J Physiol Cell Physiol. 2001;280:C1616-22 pubmed
    ..This is the first report of neurons that express two different vesicular neurotransmitter transporters in vivo...
  8. Efange S. In vivo imaging of the vesicular acetylcholine transporter and the vesicular monoamine transporter. FASEB J. 2000;14:2401-13 pubmed
    ..Similarly, in vivo studies with VAChT ligands suggest that the latter are potentially useful in detecting cholinergic lesions in vivo; however, additional development is required to fully realize the potential of these radioligands. ..
  9. Anlauf M, Schafer M, Eiden L, Weihe E. Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes. J Comp Neurol. 2003;459:90-111 pubmed
    ..The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype. ..

More Information


  1. Drolet R, Behrouz B, Lookingland K, Goudreau J. Mice lacking alpha-synuclein have an attenuated loss of striatal dopamine following prolonged chronic MPTP administration. Neurotoxicology. 2004;25:761-9 pubmed
  2. Brooks D, Frey K, Marek K, Oakes D, Paty D, Prentice R, et al. Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. Exp Neurol. 2003;184 Suppl 1:S68-79 pubmed
    ..The criteria and each of the three imaging techniques mentioned above were reviewed, and the results of that meeting are presented. ..
  3. Leroux Nicollet I, Costentin J. Transient expression of the vesicular monoamine transporter during development in the rat thalamus and cortex. Neurosci Lett. 1998;248:167-70 pubmed
    ..These data suggest that monoamine vesicular storage participates in the early postnatal maturation of thalamus and cortex. ..
  4. Erickson J, Schafer M, Bonner T, Eiden L, Weihe E. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1996;93:5166-71 pubmed
  5. Thiriot D, Sievert M, Ruoho A. Identification of human vesicle monoamine transporter (VMAT2) lumenal cysteines that form an intramolecular disulfide bond. Biochemistry. 2002;41:6346-53 pubmed
    ..We conclude that human VMAT2 Cys 126 in loop 1/2 and Cys 333 in loop 7/8 form a disulfide bond which contributes to efficient monoamine transport. ..
  6. 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. ..
  7. Habecker B, Klein M, Cox B, Packard B. Norepinephrine transporter expression in cholinergic sympathetic neurons: differential regulation of membrane and vesicular transporters. Dev Biol. 2000;220:85-96 pubmed
    ..Thus, production of NE and the transporters required for noradrenergic transmission are not coordinately regulated during cholinergic development. ..
  8. Tang Y, Nee A, Lu A, Ran R, Sharp F. Blood genomic expression profile for neuronal injury. J Cereb Blood Flow Metab. 2003;23:310-9 pubmed
  9. Fleckenstein A, Gibb J, Hanson G. Differential effects of stimulants on monoaminergic transporters: pharmacological consequences and implications for neurotoxicity. Eur J Pharmacol. 2000;406:1-13 pubmed
    ..Hence, this review will describe recent ex vivo studies investigating the rapid and differential affects of several stimulants on both plasmalemmal and vesicular monoamine transporter function. ..
  10. Carson R, Robertson D. Genetic manipulation of noradrenergic neurons. J Pharmacol Exp Ther. 2002;301:410-7 pubmed
  11. Smits S, Ponnio T, Conneely O, Burbach J, Smidt M. Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci. 2003;18:1731-8 pubmed
    ..5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function. ..
  12. Persico A, Mengual E, Moessner R, Hall F, Revay R, Sora I, et al. Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release. J Neurosci. 2001;21:6862-73 pubmed
    ..Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not. ..
  13. Tischler A. Chromaffin cells as models of endocrine cells and neurons. Ann N Y Acad Sci. 2002;971:366-70 pubmed
  14. Hussain I, Bate G, Henry J, Djali P, Dimaline R, Dockray G, et al. Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells. J Physiol. 1999;517 ( Pt 2):495-505 pubmed
    ..Dietary amines also modulate cleavage of progastrin-derived peptides, but do so by a VMAT1-independent mechanism; they may act as weak bases that passively permeate secretory vesicle membranes and raise intravesicular pH. ..
  15. Rehavi M, Roz N, Weizman A. Chronic clozapine, but not haloperidol, treatment affects rat brain vesicular monoamine transporter 2. Eur Neuropsychopharmacol. 2002;12:261-8 pubmed
    ..Haloperidol induced an increase in the serotonin transporter in the striatum and the core of the nucleus accumbens. The special effect of clozapine on VMAT(2) expression may be relevant to its unique therapeutic advantages. ..
  16. Roghani A, Welch C, Xia Y, Liu Y, Peter D, Finn J, et al. Assignment of the mouse vesicular monoamine transporter genes, Slc18a1 and Slc18a2, to chromosomes 8 and 19 by linkage analysis. Mamm Genome. 1996;7:393-4 pubmed
  17. Huynh T, Pacak K, Brouwers F, Abu Asab M, Worrell R, Walther M, et al. Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Eur J Endocrinol. 2005;153:551-63 pubmed
    ..The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines. ..
  18. Bordi C, Corleto V, Azzoni C, Pizzi S, Ferraro G, Gibril F, et al. The antral mucosa as a new site for endocrine tumors in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndromes. J Clin Endocrinol Metab. 2001;86:2236-42 pubmed
    ..These tumors did not express the phenotype of normal antral endocrine cells and, in at least two cases, were identified as ectopic ECL cell carcinoids. ..
  19. Madras B, Miller G, Fischman A. The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1397-409 pubmed
    ..Thus, ADHD medications targeting DAT or NET might disperse dopamine widely and consign dopamine storage and release to regulation by noradrenergic, as well as dopaminergic neurons. ..
  20. Sajadi A, Bauer M, Thony B, Aebischer P. Long-term glial cell line-derived neurotrophic factor overexpression in the intact nigrostriatal system in rats leads to a decrease of dopamine and increase of tetrahydrobiopterin production. J Neurochem. 2005;93:1482-6 pubmed
  21. Koerner P, Hesslinger C, Schaefermeyer A, Prinz C, Gratzl M. Evidence for histamine as a transmitter in rat carotid body sensor cells. J Neurochem. 2004;91:493-500 pubmed
    ..Our data suggest that histamine is synthesized, stored and released upon hypoxia by dopaminergic sensor cells of the rat carotid body. ..
  22. Gasior M, Paronis C, Bergman J. Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys. J Pharmacol Exp Ther. 2004;308:249-59 pubmed
    ..v. self-administration behavior engendered by priming doses of cocaine may involve actions mediated through both D1 and D2 families of dopamine receptors. ..
  23. Erickson J, Eiden L, Hoffman B. Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1992;89:10993-7 pubmed
    ..The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules. ..
  24. Amenta F, Bronzetti E, Cantalamessa F, El Assouad D, Felici L, Ricci A, et al. Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes. J Neuroimmunol. 2001;117:133-42 pubmed
    ..In view of this assessment of lymphocyte DAT and VMAT transporters can be considered for identifying pathologies characterized by impaired dopaminergic neurotransmission. ..
  25. Nakao N, Shintani Mizushima A, Kakishita K, Itakura T. The ability of grafted human sympathetic neurons to synthesize and store dopamine: a potential mechanism for the clinical effect of sympathetic neuron autografts in patients with Parkinson's disease. Exp Neurol. 2004;188:65-73 pubmed
  26. Miller G, Gainetdinov R, Levey A, Caron M. Dopamine transporters and neuronal injury. Trends Pharmacol Sci. 1999;20:424-9 pubmed
    ..DAT and VMAT2 expression can predict the selective vulnerability of neuronal populations, which suggests that therapeutic strategies aimed at altering DAT and VMAT2 function could have significant benefits in a variety of disorders. ..
  27. Kilbourn M, Sherman P. In vivo binding of (+)-alpha-[3H]dihydrotetrabenazine to the vesicular monoamine transporter of rat brain: bolus vs. equilibrium studies. Eur J Pharmacol. 1997;331:161-8 pubmed
    ..Both infusion and bolus injection methods give acceptable in vivo measures of (+)-alpha-[3H]dihydrotetrabenazine binding to the vesicular monoamine transporter of rat brain. ..
  28. Whitley J, Parsons J, Freeman J, Liu Y, Edwards R, Near J. Electrochemical monitoring of transport by a vesicular monoamine transporter expressed in Xenopus oocytes. J Neurosci Methods. 2004;133:191-9 pubmed
    ..These results suggest that expression of VMATs in oocytes may provide a useful model system for mechanistic and regulatory studies that would not be feasible using traditional methods. ..
  29. Truong J, Hanson G, Fleckenstein A. Apomorphine increases vesicular monoamine transporter-2 function: implications for neurodegeneration. Eur J Pharmacol. 2004;492:143-7 pubmed
    ..This effect of apomorphine on vesicular dopamine uptake was blocked by pretreating with eticlopride, a dopamine D2 receptor antagonist. The implications of these findings relevant to the treatment of neurodegeneration are discussed. ..
  30. Vardy E, Arkin I, Gottschalk K, Kaback H, Schuldiner S. Structural conservation in the major facilitator superfamily as revealed by comparative modeling. Protein Sci. 2004;13:1832-40 pubmed
    ..The models are based on the two MFS structures and on experimental data. The models for both proteins are in good agreement with the data available and support the notion of a shared fold for all MFS proteins. ..
  31. Fleckenstein A, Hanson G. Impact of psychostimulants on vesicular monoamine transporter function. Eur J Pharmacol. 2003;479:283-9 pubmed
    ..As described in this review, these studies not only provide insight into the pharmacological actions of stimulants, but also mechanisms underlying neurodegenerative disorders, including Parkinson's disease. ..
  32. Feng J, Cheng F, Lin C, Wei J, Yang S. Characterization of 5-HT transporter and receptor system in HeLaS3 cells by [(3)H]8-OH-DPAT and other serotonergic ligands. Arch Biochem Biophys. 2011;506:66-72 pubmed publisher
    ..These observations could help elucidate the relevant characteristics of different types of 5-HT receptors and 5-HT membrane transporters in tumor cells and their role in tumorigenesis. ..
  33. Xu W, Liu L, Mooslehner K, Emson P. Structural organization of the human vesicular monoamine transporter type-2 gene and promoter analysis using the jelly fish green fluorescent protein as a reporter. Brain Res Mol Brain Res. 1997;45:41-9 pubmed
  34. Pifl C, Agneter E, Drobny H, Sitte H, Singer E. Amphetamine reverses or blocks the operation of the human noradrenaline transporter depending on its concentration: superfusion studies on transfected cells. Neuropharmacology. 1999;38:157-65 pubmed
    ..At higher concentrations it blocks the noradrenaline transporter; in this case, the releasing action of amphetamine, like that of cocaine, is dependent on a vesicular pool of noradrenaline. ..
  35. Jousselin Hosaja M, Tobin C, Venault P, Joubert C, Chapouthier G. Effects of adrenal medulla graft on recovery of GABAergic and dopaminergic neuron deficits in mice: behavioural, pharmacological and immunohistochemical study. Behav Brain Res. 2003;140:185-93 pubmed
    ..Our results may contribute to the clarification of the beneficial effects of AM transplants in striatal function. ..
  36. Gainetdinov R, Fumagalli F, Wang Y, Jones S, Levey A, Miller G, et al. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem. 1998;70:1973-8 pubmed
  37. 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. ..
  38. Somogyi J, Baude A, Omori Y, Shimizu H, El Mestikawy S, Fukaya M, et al. GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. Eur J Neurosci. 2004;19:552-69 pubmed
    ..The presumed amino acid substrate of VGLUT3 may act on presynaptic kainate or group II metabotropic glutamate receptors. ..
  39. Wilhelm C, Johnson R, Lysko P, Eshleman A, Janowsky A. Effects of methamphetamine and lobeline on vesicular monoamine and dopamine transporter-mediated dopamine release in a cotransfected model system. J Pharmacol Exp Ther. 2004;310:1142-51 pubmed
    ..In addition, cotransfected cells can be used to determine mechanisms of simultaneous drug interactions at multiple sites. ..
  40. Schäfermeyer A, Gratzl M, Rad R, Dossumbekova A, Sachs G, Prinz C. Isolation and receptor profiling of ileal enterochromaffin cells. Acta Physiol Scand. 2004;182:53-62 pubmed
    ..We purified EC cells from the rat ileum by a combination of elutriation and density gradient centrifugation in order to characterize the function of this important cell type...
  41. Hogan K, Staal R, Sonsalla P. Analysis of VMAT2 binding after methamphetamine or MPTP treatment: disparity between homogenates and vesicle preparations. J Neurochem. 2000;74:2217-20 pubmed
    ..Furthermore, the changes in [H]DTBZ binding in homogenates may not be a sensitive indicator of early damage to synaptic vesicles, although homogenate binding reliably identifies a loss of VMAT2 at later times. ..
  42. Watson F, Kiernan R, Deavall D, Varro A, Dimaline R. Transcriptional activation of the rat vesicular monoamine transporter 2 promoter in gastric epithelial cells: regulation by gastrin. J Biol Chem. 2001;276:7661-71 pubmed
  43. Surratt C, Persico A, Yang X, Edgar S, Bird G, Hawkins A, et al. A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifications, reveals chromosome 10 gene localization and identifies TaqI RFLPs. FEBS Lett. 1993;318:325-30 pubmed
    ..The cDNA, and a subclone, recognize TaqI polymorphisms that may prove useful to assess this gene's involvement in neuropsychiatric disorders involving monoaminergic brain systems. ..
  44. Krantz D, Peter D, Liu Y, Edwards R. Phosphorylation of a vesicular monoamine transporter by casein kinase II. J Biol Chem. 1997;272:6752-9 pubmed
    ..These results provide the first demonstration of phosphorylation of a vesicular neurotransmitter transporter and a potential mechanism for differential regulation of the two VMATs. ..
  45. Jaber M, Dumartin B, Sagne C, Haycock J, Roubert C, Giros B, et al. Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. Eur J Neurosci. 1999;11:3499-511 pubmed
    ..The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition. ..
  46. 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. ..
  47. Guilarte T, Nihei M, McGlothan J, Howard A. Methamphetamine-induced deficits of brain monoaminergic neuronal markers: distal axotomy or neuronal plasticity. Neuroscience. 2003;122:499-513 pubmed
    ..However, the DAT and 5-HTT deficits in brain regions lacking a deficit in VMAT-2 and glial cell activation may reflect drug-induced modulation of these plasma membrane proteins. ..
  48. Hall F, Sora I, Uhl G. Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice. Neuropsychopharmacology. 2003;28:620-8 pubmed
    ..Thus, lifetime reductions in the expression of either DAT or VMAT2 increase ethanol consumption, dependent on sex. ..
  49. Travis E, Wang Y, Michael D, Caron M, Wightman R. Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice. Proc Natl Acad Sci U S A. 2000;97:162-7 pubmed
    ..Thus, although vesicular transport is the limiting factor determining quantal size of 5-HT and histamine release, intragranular association with the heparin matrix also plays a significant role. ..
  50. Nilsson O, Jakobsen A, Kölby L, Bernhardt P, Forssell Aronsson E, Ahlman H. Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Ann N Y Acad Sci. 2004;1014:280-3 pubmed
    ..It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy. ..
  51. Misbahuddin A, Placzek M, Taanman J, Gschmeissner S, Schiavo G, Cooper J, et al. Mutant torsinA, which causes early-onset primary torsion dystonia, is redistributed to membranous structures enriched in vesicular monoamine transporter in cultured human SH-SY5Y cells. Mov Disord. 2005;20:432-40 pubmed
    ..Abnormal processing, transport, or entrapment of VMAT2 within the mutant torsinA membranous inclusions, therefore, may affect cellular dopamine release, providing a potential pathogenic mechanism for the DYT1-dependent dystonia. ..
  52. Stahl S, Shayegan D. The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12 pubmed
    ..Efficacy and tolerability data from trials to date indicate that ziprasidone's clinical activity is consistent with its receptor profile. ..
  53. Höltje M, Winter S, Walther D, Pahner I, Hörtnagl H, Ottersen O, et al. The vesicular monoamine content regulates VMAT2 activity through Galphaq in mouse platelets. Evidence for autoregulation of vesicular transmitter uptake. J Biol Chem. 2003;278:15850-8 pubmed
    ..It is concluded that in platelets the vesicle itself regulates transmitter transporter activity via its content and vesicle-associated Galpha(q). ..