Skip to main content
SpringerLink
Log in

The Vesicular Monoamine Transporters (VMATs): Role in the Chemical Coding of Neuronal Transmission and Monoamine Storage in Amine-Handling Immune and Inflammatory Cells

  • Chapter
Catecholamine Research

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 53))

Abstract

Monoamines can act as neurotransmitters, hormones, autocrine and paracrine factors, or autacoids. How they function depends on the locations of the cells that synthesize and store them, and the stimuli that release them. All amine transmitters are first sequestered in a storage vesicle or granule, from which they are secreted from the cell. This requires specific transporters that reside on the vesicle. All of the vesicular transporters for classical neurotransmitters inferred to exist as individual proteins based on functional studies, have been cloned and characterized in a detailed molecular way over the last ten years (see Table 1). As a result, an understanding has developed that the role of these transporters in the chemical coding of neurotransmission is dynamic, and a novel view of what constitutes a neurotransmitter phenotype for a given neuron has emerged. The purpose of this contribution is to highlight recent progress from our laboratories and others in understanding the evolution of vesicular transporter structure, transport properties and cell-specific expression, as these relate to the physiological and regulatory functions of mammalian monoamine-containing*** neuronal, endocrine, and hematopoietic cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. B. I. Kanner and S. Schuldiner, Mechanism of transport and storage of neurotransmitters, CRC Crit. Rev. Biochem. 22, 1–38 (1987).

    Article  PubMed  CAS  Google Scholar 

  2. R. G. Johnson Jr., Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport, Physiol. Revs. 68, 232–307 (1988).

    CAS  Google Scholar 

  3. P. R. Maycox, T. Deckwoerth, J. W. Hell, and R. Jahn, Glutamate uptake by brain synaptic vesicles, J. Biol. Chem. 263, 15423–15428 (1988).

    PubMed  CAS  Google Scholar 

  4. P. M. Burger, J. Hell, E. Mehl, C. Krasel, F. Lottspeich, and R. Jahn, GABA and glycine in synaptic vesicles: Storage and transport characteristics, Neuron 7, 287–293 (1991).

    Article  PubMed  CAS  Google Scholar 

  5. S. M. Parsons, Transport mechanisms in acetylcholine and monoamine storage, FASEB J. 14, 2423–2434 (2000).

    Article  PubMed  CAS  Google Scholar 

  6. B. Rost, PHD: predicting one-dimensional protein structure by profile based neural networks, Meth. Enzymol. 266,525–539 (1996).

    Article  PubMed  CAS  Google Scholar 

  7. B. Rost, P. Fariselli, and R. Casadio, Topology prediction for helical transmembrane proteins at 86% accuracy, Protein Science 7, 1704–1718 (1996).

    Article  Google Scholar 

  8. M. L. Gilmor, N. R. Nash, A. Roghani, R. H. Edwards, H. Yi, S. M. Hersch, and A. I. Levey, Expression of the putative vesicular acetylcholine transporter in rat brain and localization in cholinergic synaptic vesicles, J. Neurosci. 16, 2179–2190 (1996).

    PubMed  CAS  Google Scholar 

  9. E. Weihe, J.-H. Tao-Cheng, M. K.-H. Schäfer, J. D. Erickson, and L. E. Eiden, Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles, Proc. Natl. Acad. Sci. USA 93, 3547–3552 (1996).

    Article  PubMed  CAS  Google Scholar 

  10. S. Schuldiner, A. Shirvan, and M. Linial, Vesicular neurotransmitter transporters: From bacteria to humans, Physiol. Rev. 75, 369–392 (1995).

    PubMed  CAS  Google Scholar 

  11. C. Sagné, S. E. Mestikaway, M.-F. Isambert, M. Hamon, J.-P. Nenry, B. Giros, and B. Gasnier, Cloning of a functional vesicular GABA and glycine transporter by screening of genome databases, 417, 177–183(1997).

    Google Scholar 

  12. S. L. McIntire, R. J. Reimer, K. Schuske, R. H. Edwards, and E. M. Jorgensen, Identification and characterization of the vesicular GABA transporter, Nature 389, 870–876 (1997).

    Article  PubMed  CAS  Google Scholar 

  13. E. E. Bellochio, R. J. Reimer, R. T. Fremeau Jr., and R. H. Edwards, Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter, Science 289, 957–960 (2000).

    Article  Google Scholar 

  14. S. Takamori, J. S. Rhee, C. Rosenmund, and R. Jahn, Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons, Nature 407, 189–194 (2000).

    Article  PubMed  CAS  Google Scholar 

  15. J. D. Erickson, L. E. Eiden, and B. Hoffman, Expression cloning of a reserpine-sensitive vesicular monoamine transporter, Froc. Natl. Acad. Sci. USA 89, 10993–10997 (1992).

    Article  CAS  Google Scholar 

  16. Y. Liu, D. Peter, A. Roghani, S. Schuldiner, G. G. Prive, D. Eisenberg, N. Brecha, and R. H. Edwards, A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter, Cell 70, 539–551 (1992).

    Article  PubMed  CAS  Google Scholar 

  17. A. Alfonso, K. Grundahl, J. R. McManus, and J. B. Rand, Cloning and characterization of the choline acetyltransferase structural gene (cha-1) from C. elegans, J. Neurosci. 14, 2290–3300 (1994).

    PubMed  CAS  Google Scholar 

  18. J. D. Erickson, H. Varoqui, M. Schäfer, M.-F. Diebler, E. Weihe, W. Modi, J. Rand, L. E. Eiden, T. I. Bonner, and T. Usdin, Functional characterization of the mammalian vesicular acetylcholine transporter and its expression from a ‘cholinergic’ gene locus, J. Biol. Chem. 269, 21929–21932 (1994).

    PubMed  CAS  Google Scholar 

  19. S. Schuldiner, A molecular glimpse of vesicular transporters, J. Neurochem. 62, 2067–2078 (1994).

    Article  PubMed  CAS  Google Scholar 

  20. M. K.-H. Schäfer, B. Schütz, E. Weihe, and L. E. Eiden, Target-independent cholinergic differentiation in the rat sympathetic nervous system, Proc. Natl. Acad. Sci. USA 94, 4149–4154 (1997).

    Article  PubMed  Google Scholar 

  21. B. Schütz, M. K.-H. Schäfer, L. E. Eiden, and E. Weihe, Vesicular amine transporter expression and isoform selection in developing brain, peripheral nervous system and gut, Dev. Brain Res. 106, 181–204 (1998).

    Article  Google Scholar 

  22. S. E. Asmus, S. Parsons, and S. C. Landis, Developmental changes in the transmitter properties of sympathetic neurons that innervate the periosteum, J. Neurosci. 20, 1495–1504 (2000).

    PubMed  CAS  Google Scholar 

  23. C. Goridis and J.-F. Brunet, Transcriptional control of neurotransmitter phenotype, Curr. Opin. Neurobiol. 9,47–53(1999).

    Article  PubMed  CAS  Google Scholar 

  24. D. Frisby, J. McManus, J. Duerr, and J. Rand, Regulation of cholinergic gene expression in C. elegans, Soc. Neurosci. Abstr. 22, 1032 (1996).

    Google Scholar 

  25. C. Eastman, H. R. Horvitz, and Y. S. Jin, Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-30 homeodomain protein, J. Neurosci. 9, 6225–6234 (1999).

    Google Scholar 

  26. J. J. Westmoreland, J. McEwen, B. A. Moore, Y. Jin, and B. G. Condie, Conserved function of C. elegans UNC-30 and mouse Pitx2 in controlling GABAergic neuron differentiation, J. Neurosci. in press, (2001).

    Google Scholar 

  27. M.-R. Hirsch, M.-C. Tiveron, F. Guillemot, J.-F. Brunet, and C. Goridis, Control of noradrenergic differentiation and Phox2a expression by MASH1 in the central and peripheral nervous system, Development 125, 599–608 (1998).

    PubMed  CAS  Google Scholar 

  28. L. Lo, M.-C. Tiveron, and D. J. Anderson, MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity, Development 125, 609–620 (1998).

    PubMed  CAS  Google Scholar 

  29. J.-F. Brunet and A. Ghysen, Deconstructing cell determination: proneural genes and neuronal identity, Bio Essays 21, 313–318 (1999).

    CAS  Google Scholar 

  30. C. Yang, H.-S. Kim, H. Seo, C.-H. Kim, J.-F. Brunet, and K.-S. Kim, Paired-like homeodomain proteins, Phox2a and Phox2B., are responsible for noradrenergic cell-specific transcription of the dopamine ß- hydroxylase gene, J. Neurochem. 71, 1813–1826 (1998).

    Article  PubMed  CAS  Google Scholar 

  31. M. Adachi, D. Browne, and E. J. Lewis, Paired-like homeodomain proteins Phox2a/Arix and Phox2b/NBPhox have similar genetic organization and independently regulate dopamine ß-hydroxylase gene transcription, DNA Cell Biol. 19, 539–554 (2000).

    Article  PubMed  CAS  Google Scholar 

  32. C.-H. Kim, H.-S. Kim, J. F. Cubells, and K.-S. Kim, A previously undescribed intron and extensive 5’ upstreamm sequence, but not Phox2a-mediated transactivation, are necessary for high level cell type- specific expression of the human norepinephrine transporter gene, J. Biol. Chem. 274, 6507–6518 (1999).

    Article  PubMed  CAS  Google Scholar 

  33. J. D. Erickson, M. K.-H. Schäfer, T. I. Bonner, L. E. Eiden, and E. Weihe, 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, 5166–5171 (1996).

    Article  PubMed  CAS  Google Scholar 

  34. D. Peter, J. Jimenez, Y. Liu, J. Kim, and R. H. Edwards, The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors, J. Biol. Chem. 269, 7231–7237 (1994).

    PubMed  CAS  Google Scholar 

  35. E. Weihe, M. K.-H. Schäfer, J. D. Erickson, and L. E. Eiden, Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat, J. Mol. Neurosci. 5, 149–164 (1994).

    Article  PubMed  CAS  Google Scholar 

  36. J. D. Erickson, L. E. Eiden, M. K.-H. Schäfer, and E. Weihe, Reserpine- and tetrabenazine-sensitive transport of 3H-histamine by the neuronal isoform of the vesicular monoamine transporter, J. Mol. Neurosci. 6, 277–287 (1995).

    Article  PubMed  CAS  Google Scholar 

  37. A. Merickel and R. H. Edwards, Transport of histamine by vesicular monoamine transporter-2, Neuropharmacol 34, 1543–1547 (1995).

    Article  CAS  Google Scholar 

  38. J. S. Duerr, D. L. Frisby, J. Gaskin, A. Duke, K. Asermely, D. Huddleston, L. E. Eiden, and J. B. Rand, The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors, J. Neurosci. 19, 72–84 (1999).

    PubMed  CAS  Google Scholar 

  39. C. McClung and J. Hirsh, The trace amine tyramine is essential for sensitization to cocaine in Drosophila, Curr. Biol. 9, 853–860 (1999).

    Article  PubMed  CAS  Google Scholar 

  40. M. Monastirioti, C. E. Linn, and K. White, Characterization of Drosophila tyramine beta-hydroxylase gene and isolation of mutant flies lacking octopamine, J. Neurosci. 16, 3900–3911 (1996).

    PubMed  CAS  Google Scholar 

  41. J. F. Tallman, J. M. Saavedra, and J. Axelrod, Biosynthesis and metabolism of endogenous tyramine and its normal presence in sympathetic nerves, J. Pharmacol. Exp. Ther. 199, 216–221 (1976).

    PubMed  CAS  Google Scholar 

  42. J. B. Rand, J. S. Duerr, and D. L. Frisby, Neurogenetics of vesicular transporters in C. elegans, FASEB J. 14,2414–2422(2000).

    Article  PubMed  CAS  Google Scholar 

  43. M. A. Paulos and R. E. Tessel, Excretion of beta-phenethylamine is elevated in humans after profound stress, Science 215, 1127–1129 (1982).

    Article  PubMed  CAS  Google Scholar 

  44. E. Weihe and L. E. Eiden, Vesicular amine transporter expression in amine-handling cells of the nervous, endocrine and inflammatory systems, FASEB J. 14, 2435–2449 (2000).

    Article  PubMed  CAS  Google Scholar 

  45. E. Blaugrund, T. D. Pham, V. M. Tennyson, L. Lo, L. Sommer, D. J. Anderson, and M. D. Gershon, Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1 dependence, Development 122, 309–320 (1996).

    PubMed  CAS  Google Scholar 

  46. C. Lebrand, O. Cases, C. Adelbrecht, A. Doye, C. Alvarez, S. El Mestikawy, I. Scif, and P. Gaspar, Transient uptake and storage of serotonin in developing thalamic neurons, Neuron 17, 823–835 (1996).

    Article  PubMed  CAS  Google Scholar 

  47. K. Kitahama, N. Sakamoto, A. Jouvet, I. Nagatsu, and J. Pearson, Dopamine-beta-hydroxylase and tyrosine hydroxylase immunoreactive neurons in the human brainstem, J. Chem. Neuroanat. 10, 137–146 (1996).

    Article  PubMed  CAS  Google Scholar 

  48. E. Weihe and L. E. Eiden, Chemical neuroanatomy of the vesicular transporters, FASEB J. 14, 2435–2449 (2000).

    Article  PubMed  CAS  Google Scholar 

  49. I. S. Balan, M. V. Ugrumov, A. Calas, P. Mailly, M. Kreiger, and J. Thibault, Tyrosine hydroxylase- expressing and/or aromatic L-amino acid decarboxylase-expressing neurons in the mediobasal hypothalamus of perinatal rats: differentiation and sexual dimorphism, J. Comp. Neurol. 425, 167–176 (2000).

    Article  PubMed  CAS  Google Scholar 

  50. G. Guidry and S. C. Landis, Target-dependent development of the vesicular acetylcholine transporter in rodent sweat gland innervation, Dev. Biol. 199, 175–184 (1998).

    Article  PubMed  CAS  Google Scholar 

  51. S. A. Shields, K. A. MacDowell, S. B. Fairchild, and M. L. Campbell, Is mediation of sweating cholinergic, adrenergic, or both-A comment on the literature, Psychophysiology 24, 312–319 (1987).

    Article  PubMed  CAS  Google Scholar 

  52. E. Weihe, M. Anlauf, M.-K. H. Schäfer, W. Hartschuh, and L. E. Eiden, VMAT2 is the transporter mediating sequestration of monoamines in rat and human platelets, mast cells, and cutaneous dendritic cells, Soc. Neurosci. Abstr. Nov. 7–12, #301.301 (1998).

    Google Scholar 

  53. M. da Prada, A. Pletscher, J. P. Tranzer, and H. Knuchel, Subcellular localization of 5-hydroxytryptamine and histamine in blood platelets, Nature 216, 1315–1317 (1967).

    Article  PubMed  Google Scholar 

  54. M. H. Fukami, H. Holmsen, and K. Ugurbil, Histamine uptake in pig platelets and isolated dense granules, iochem. Pharmacol. 33, 3869–3874 (1984).

    Article  CAS  Google Scholar 

  55. A. Pletscher, M. Da Prada, K. H. Berneis, H. Steffen, B. Liitold, and H. G. Weder, Molecular organization f amine storage organelles of blood platelets and adrenal medulla, in Advances in Cytopharmacology, Ceccarelli, F. Clementi, and J. Meldolesi, Editors. 1974, Raven Press: New York. p. 257–264.

    Google Scholar 

  56. S. Tao-Cheng and L. E. Eiden, The vesicular monoamine transporter VMAT2 is targeted to large dense- ore vesicles, and the vesicular acetylcholine transporter VAChT to small synaptic vesicles, in PC 12 cells, Adv. Pharmacol. 42, 250–253 (1998).

    Article  PubMed  CAS  Google Scholar 

  57. J. D. Erickson, D. Yao, H. Zhu, H. Ming, and H. Varoqui, Domains of vesicular amine transporters mportant for substrate recognition and targeting to secretory organelles, FASEB J. 14, 2450–2458 (2000).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section on Molecular Neuroscience, National Institute of Mental Health, NIH, Bethesda, MD, 20892, USA

    L. E. Eiden & E. Weihe

  2. Institute of Anatomy and Cell Biology, Philipps-Universität, Marburg, Germany

    B. Schütz, M. Anlauf, C. Depboylu & M. K.-H. Schäfer

Authors
  1. L. E. Eiden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Schütz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Anlauf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Depboylu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. K.-H. Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Weihe
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fujita Health University, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  2. Nagoya University, Nagoya, Japan

    Toshitaka Nabeshima

  3. Vanderbilt University, Nashville, Tennessee, USA

    Richard McCarty

  4. National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA

    David S. Goldstein

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Eiden, L.E., Schütz, B., Anlauf, M., Depboylu, C., Schäfer, M.KH., Weihe, E. (2002). The Vesicular Monoamine Transporters (VMATs): Role in the Chemical Coding of Neuronal Transmission and Monoamine Storage in Amine-Handling Immune and Inflammatory Cells. In: Nagatsu, T., Nabeshima, T., McCarty, R., Goldstein, D.S. (eds) Catecholamine Research. Advances in Behavioral Biology, vol 53. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3538-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-3538-3_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3388-1

  • Online ISBN: 978-1-4757-3538-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation