Skip to main content
SpringerLink
Log in

Vesicular neurotransmitter transporters

Potential sites for the regulation of synaptic function

  • Original Articles
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neurotransmission depends on the regulated release of chemical transmitter molecules. This requires the packaging of these substances into the specialized secretory vesicles of neurons and neuroendocrine cells, a process mediated by specific vesicular transporters. The family of genes encoding the vesicular transporters for biogenic amines and acetylcholine have recently been cloned. Direct comparison of their transport characteristics and pharmacology provides information about vesicular transport bioenergetics, substrate feature recognition by each transporter, and the role of vesicular amine storage in the mechanism of action of psychopharmacologic and neurotoxic agents. Regulation of vesicular transport activity may affect levels of neurotransmitter available for neurosecretion and be an important site for the regulation of synaptic function. Gene knockout studies have determined vesicular transport function is critical for survival and have enabled further evaluation of the role of vesicular neurotransmitter transporters in behavior and neurotoxicity. Molecular analysis is beginning to reveal the sites involved in vesicular transporter function and the sites that determine substrate specificity. In addition, the molecular basis for the selective targeting of these transporters to specific vesicle populations and the biogenesis of monoaminergic and cholinergic synaptic vesicles are areas of research that are currently being explored. This information provides new insights into the pharmacology and physiology of biogenic amine and acetylcholine vesicular storage in cardiovascular, endocrine, and central nervous system function and has important implications for neurodegenerative disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agoston D. V., Conlon J. M., and Whittaker V. P. (1988) Selective depletion of the acetylcholine and vasoactive intestinal polypeptide of the guinea-pig myenteric plexus by differential mobilization of distinct transmitter pools.Exp. Brain Res. 72, 535–542.

    Article  PubMed  CAS  Google Scholar 

  • Alfonso A., Grundahl K., Duerr J. S., Han H.-P., and Rand J. B. (1993) TheCaenorhabditis elegans unc17 gene: a putative vesicular acetylcholine transporter.Science 261, 617–619.

    Article  PubMed  CAS  Google Scholar 

  • Alfonso A., Grundahl K., McManus J. R., Asbury J. M., and Rand J. B. (1994) Alternative splicing leads to two cholinergic proteins inCaenorhabditis elegans.J. Mol. Biol. 241, 627–630.

    Article  PubMed  CAS  Google Scholar 

  • Amara S. and Kuhar M. J. (1992) Neurotransmitter transporters—recent progress.Ann. Rev. Neurosci. 16, 73–93.

    Article  Google Scholar 

  • Ando M., Iwata M., Takahama K., and Nagata Y. (1987) Effects of extracellular choline concentration and K+ depolarization on choline kinase and choline acetyltranserase activities in superior cervical sympathetic ganglia excised from rats.J. Neurochem. 48, 1448–1453.

    Article  PubMed  CAS  Google Scholar 

  • Asher S. W. and Aminoff M. J. (1981) Tetrabenazine and movement disorders.Neurology 31, 1051–1054.

    PubMed  CAS  Google Scholar 

  • Arvidsson U., Riedl M., Elde R., and Meister B. (1997) Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker for cholinergic neurons in the central and peripheral nervous systems.J. Comp. Neurol. 378, 454–467.

    Article  PubMed  CAS  Google Scholar 

  • Axelrod J. (1971) Noradrenaline: fate and control of its biosynthesis.Science 173, 598–606.

    Article  PubMed  CAS  Google Scholar 

  • Bahr B. A. and Parsons S. M. (1986) Acetylcholine transport and drug inhibition kinetics inTorpedo synaptic vesicles.J. Neurochem. 46, 1214–1218.

    Article  PubMed  CAS  Google Scholar 

  • Bauerfeind R., Regnier-Vigouroux A., Flatmark T., and Huttner W. B. (1993) Selective storage of acetylcholine, but not catecholamines, in neuroendocrine synaptic-like microvesicles of early endosomal origin.Neuron 11, 105–121.

    Article  PubMed  CAS  Google Scholar 

  • Bauerfeind R., Jelinek R., Hellwig A., and Huttner W. B. (1995) Neurosecretory vesicles can be hybrids of synaptic vesicles and secretory granules.Proc. Natl. Acad. Sci. USA 92, 7342–7346.

    Article  PubMed  CAS  Google Scholar 

  • Béjanin S., Cervini R., Mallet J., and Berrard S. (1994) A unique gene organization for two cholinergic markers, choline acetyltransferase and a putative vesicular transporter of acetylcholine.J. Biol. Chem. 269, 21,944–21,947.

    Google Scholar 

  • Ben-Shachar D., Zuk R., and Glinka Y. (1995) Dopamine neurotoxicity: inhibition of mitochondrial respiration.J. Neurochem. 64, 718–723.

    Article  PubMed  CAS  Google Scholar 

  • Bennett M. K. and Scheller R. H. (1994) A molecular description of synaptic vesicle membrane trafficking.Ann. Rev. Biochem. 63, 63–100.

    Article  PubMed  CAS  Google Scholar 

  • Berrard S., Varoqui H., Cervini R., Israël M., Mallett J., and Diebler M.-F. (1995) Coregulation of two embedded gene products, choline acetyltransferase and the vesicular acetylcholine transporter.J. Neurochem.,65, 939–942.

    Article  PubMed  CAS  Google Scholar 

  • Berse B. and Blusztajn J. K. (1995) Coordinated up-regulation of choline acetyltransferase and vesicular acetylcholine transporter gene expression by the retinoic acid receptor α, cAMP, and leukemia inhibitory factor/ciliary neurotrophic factor signaling pathways in a murine septal cell line.J. Biol. Chem. 270, 22,101–22,104.

    CAS  Google Scholar 

  • Blumberg D. and Schweitzer E. S. (1992) Vesamicol binding to subcellular membranes that are distinct from catecholaminergic vesicles in PC12 cells.J. Neurochem. 58, 801–810.

    Article  PubMed  CAS  Google Scholar 

  • Blusztajn J. K. and Wurtman R. J. (1983) Choline and cholinergic neurons.Science 221, 614–619.

    Article  PubMed  CAS  Google Scholar 

  • Boissière F., Faucheux B., Agid Y., and Hirsch E. C. (1997) Choline acetyltransferase mRNA expresion in the striatal neurons of patients with Alzheimer's disease.Neurosci. Lett. 225, 169–172.

    Article  PubMed  Google Scholar 

  • Brenner S. (1974) The genetics of Caenorhabditis elegans.Genetics 77, 71–94.

    PubMed  CAS  Google Scholar 

  • Buu N. T. (1989) Modification of vesicular dopamine and norepinephrine by monoamine oxidase inhibitors.Biochem. Pharmacol. 38, 1685–1692.

    Article  PubMed  CAS  Google Scholar 

  • Cameron P. L., Sudhof T. C., Jahn R., and de Camilli P. (1991) Colocalization of synaptophysin with transferrin receptors: implications for synaptic vesicle biogenesis.J. Cell Biol. 115, 151–164.

    Article  PubMed  CAS  Google Scholar 

  • Cervini R., Berrard S., Béjanin S., and Mallet J. (1994) Regulation by CDF/LIF and retinoic acid of multiple ChAT mRNAs produced from distinct promoters.NeuroReport 5, 1346–1348.

    PubMed  CAS  Google Scholar 

  • Cervini R., Houhou L., Pradat P.-F., Béjanin S., Mallet, J., and Berrard S. (1995) Specific vesicular acetylcholine transporter promoters lie within the first intron of the rat choline acetyltransferase gene.J. Biol. Chem. 270, 24,654–24,657.

    CAS  Google Scholar 

  • Clarkson E., Rogers G., and Parsons S. (1992) Binding and active transport of large analogues of acetylcholine by cholinergic synaptic vesicles in vitro.J. Neurochem. 59, 695–700.

    Article  PubMed  CAS  Google Scholar 

  • Clift-O'Grady L., Linstedt A. D., Lowe A. W., Grote E., and Kelly R. B. (1990) Biogenesis of synaptic vesicle-like structures in a pheochromocytoma cell line PC-12.J. Cell Biol. 110, 1693–1703.

    Article  PubMed  Google Scholar 

  • Cohen E. L. and Wurtman R. J. (1975) Brain acetylcholine: increase after systemic choline administration.Life Sci. 16, 1095–1102.

    Article  PubMed  CAS  Google Scholar 

  • Costa D. and Sandler M., eds. (1972)Monoamine Oxidases—New Vistas. Advances in Biochemical Psychopharmacology, vol. 5, Raven, New York.

    Google Scholar 

  • Cubells J. F., Rayport S., Rajendran G., and Sulzer D. (1994) Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress.J. Neurosci. 14, 2260–2271.

    PubMed  CAS  Google Scholar 

  • Darchen F., Scherman D., Desnos C., and Henry J.-P. (1988) Characteristics of the transport of the quaternary ammonium 1-methyl-4-phenyl-pyridinium by chromaffin granules.Biochem. Pharmacol. 37, 4381–4387.

    Article  PubMed  CAS  Google Scholar 

  • Darchen F., Scherman D., and Henry J.-P. (1989) Reserpine binding to chromaffin granules suggests the existence of two conformations of the monoamine transporter.Biochemistry 28, 1692–1697.

    Article  PubMed  CAS  Google Scholar 

  • Davies P. and Maloney A. J. P. (1976) Selective loss of cholinergic neurons in Alzheimer's disease.Lancet 2, 1403.

    Article  PubMed  CAS  Google Scholar 

  • Davis G. C., Williams A. C., Markey S. P., Ebert M. H., Caine E. D., Reichert C. M., and Kopin I. J. (1979) Chronic Parkinsonism secondary to intravenous injection of meperidine analogues.Psychiatry Res. 1, 249–254.

    Article  PubMed  CAS  Google Scholar 

  • De Giorgio R., Su D., Peter D., Edwards R. H., Brecha N. C., and Sternini C. (1996) Vesicular monoamine transporter 2 expression in enteric neurons and enterochromaffin-like cells of the rat.Neurosci Lett. 217, 77–80.

    Article  PubMed  Google Scholar 

  • Desnos C., Laran M. P., and Scherman D. (1992) Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus biosynthesis coupling.J. Neurochem. 59, 2105–2112.

    Article  PubMed  CAS  Google Scholar 

  • Desnos C., Laran M.-P., Langley K., Aunis D., and Henry J.-P. (1995) Long term stimulation changes the vesicular monoamine transporter content of chromaffin granules.J. Biol. Chem. 270, 16,030–16,038.

    CAS  Google Scholar 

  • Diebler M. F. and Morot Gaudry-Talarmain Y. (1989) AH5183 and cetiedil: two potent inhibitors of acetylcholine uptake into synaptic vesicles fromTorpedo marmorata.J. Neurochem. 52, 813–821.

    Article  PubMed  CAS  Google Scholar 

  • Diebler M. F. (1992) Effect of N-N′-dicyclohexylcarbodiimide on the binding of vesamicol, an inhibitor of acetylcholine transport into synaptic vesicles.Neurochem. Int. 21, 83–90.

    Article  PubMed  CAS  Google Scholar 

  • Dimaline R. and Struthers J. (1996) Expression and regulation of a vesicular monoamine transporter in rat stomach: a putative histamine transporter.J. Physiol. 490, 249–256.

    PubMed  CAS  Google Scholar 

  • Disbrow J. K., Gershten M. J., and Ruth J. A. (1983) Immobilization of rat brain synaptic vesicles on positively-charged glass microspheres.Experientia 39, 623–625.

    Article  PubMed  CAS  Google Scholar 

  • Dyrks T., Weidemann A., Multhaup G., Salbaum J. M., Lemaire H.-G., Kang J., Müller-Hill B., Masters C. L., and Beyreuther K. (1988) Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.EMBO J. 7, 949–957.

    PubMed  CAS  Google Scholar 

  • Erickson J. D., Masserano J. M., Barnes E. M., Ruth J. A., and Weiner N. (1990) Chloride ion increases [3H]dopamine accumulation by synaptic vesicles purified from rat striatum: inhibition by thiocyanate ion.Brain Res. 516, 155–160.

    Article  PubMed  CAS  Google Scholar 

  • Erickson J. D., Eiden L. E., and Hoffman B. (1992) Expression cloning of a reserpine-sensitive vesicular monoamine transporter.Proc. Natl. Acad. Sci. USA 89, 10,993–10,997.

    Article  CAS  Google Scholar 

  • Erickson J. D. and Eiden L. E. (1993) Functional identification and molecular cloning of a human brain vesicle monoamine transporter.J. Neurochem. 61, 2314–2317.

    Article  PubMed  CAS  Google Scholar 

  • Erickson J. D., Varoqui H., Schäfer M. K.-H., Diebler M.-F., Weihe E., Modi W., Rand J. B., Eiden L. E., Bonner T. I., and Usdin T. (1994) Functional characterization of the mammalian vesicular acetylcholine transporter and its expression from a ‘cholinergic’ gene locus.J. Biol. Chem. 269, 21,929–21,932.

    CAS  Google Scholar 

  • Erickson J. D., Eiden L. E., Schäfer M. K.-H., and Weihe E. (1995) Reserpine-and tetrabenazinesensitive transport of3H-histamine by the neuronal isoform of the vesicular monoamine transporter.J. Mol. Neurosci. 6, 277–287.

    Article  PubMed  CAS  Google Scholar 

  • Erickson J. D., Schäfer M. K.-H., Bonner T. I., Eiden L. E., and Weihe E. (1996a) 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.

    Article  PubMed  CAS  Google Scholar 

  • Erickson J. D., Weihe E., Schäfer J. K.-M., Neale E., Williamson L., Bonner T. I., Tao-Cheng J.-H., and Eiden L. E. (1996b) The VAChT/ChAT ‘cholinergic gene locus’: new aspects of genetic and vesicular regulation of cholinergic function.Prog. Brain Res. 109, 69–82.

    PubMed  CAS  Google Scholar 

  • Erickson, J. D. (1997) A chimeric vesicular monoamine transporter dissociates sensitivity to tetrabenazine and unsubstituted aromatic amines.Adv. Pharmacol., in press.

  • Fahn S. and Cohen G. (1992) The oxidant stress hypothesis in Parkinson's disease: evidence supporting it.Ann. Neurol. 32, 804–812.

    Article  PubMed  CAS  Google Scholar 

  • Feany M. B., Yee A. G., Delvy M. L., and Buckley K. M. (1993) The synaptic vesicle proteins SV2, synaptotagmin and synaptophysin are sorted to separate cellular compartments in CHO fibroblasts.J. Cell Biol. 123, 575–584.

    Article  PubMed  CAS  Google Scholar 

  • Floor E., Leventhal P. S., Wang Y., Meng L., and Chen W. (1995) Dynamic storage of dopamine in rat brain synaptic vesicles in vitro.J. Neurochem. 64, 689–699.

    Article  PubMed  CAS  Google Scholar 

  • Frize E. D. (1954) Mental depression in hypertensive patients treated for long periods with high doses of reserpine.N. Engl. J. Med. 251, 1006–1008.

    Article  Google Scholar 

  • Gasnier B., Scherman D., and Henry J.-P. (1985) Dicyclohexylcarbodiimide inhibits the monoamine carrier of bovine chromaffin granule membrane.Biochemistry 24, 1239–1244.

    Article  PubMed  CAS  Google Scholar 

  • Gasnier B., Krejci E., Botton D., Massoulié J., and Henry J.-P. (1994) Expression of a bovine vesicular monoamine transporter in COS cells.FEBS Lett. 342, 225–229.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Green L. A. and Rein G. (1977a) Synthesis, storage, and release of acetylcholine by a noradrenergic pheochromocytoma cell line.Nature 268, 349–351.

    Article  Google Scholar 

  • Green L. A. and Rein G. (1977b) Release, storage, and uptake of catecholamines by a clonal cell line of nerve growth factor (NGF) responsive pheochromocytoma cells.Brain Res. 129, 247–263.

    Article  Google Scholar 

  • Grote E., Hao J. C., Bennett M. K., and Kelly R. B. (1995) A targeting signal in VAMP regulating transport to synaptic vesicles.Cell 81, 581–589.

    Article  PubMed  CAS  Google Scholar 

  • Geula C. and Mesulam M. M. (1989) Cortical cholinergic fibers in ageing and Alzheimer's disease: a morphometric study.Neuroscience 33, 469–476.

    Article  PubMed  CAS  Google Scholar 

  • Harrington K. A., Augood S. J., Kingsbury A. E., Foster O. J. F., and Emson P. C. (1996) Dopamine transporter (DAT) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson's disease.Mol. Brain Res 36, 157–162.

    Article  PubMed  CAS  Google Scholar 

  • Henry J.-P., Gasnier B., Roisin M. P., Isambert M.-F., and Scherman D. (1987) Molecular pharmacology of the monoamine transporter of the chromaffin granule membrane.Ann. NY Acad. Sci. 493, 194–206.

    Article  PubMed  CAS  Google Scholar 

  • Henry J.-P. and Scherman D. (1989) Radioligands of the vesicular monoamine transporter and their use as markers of the monoamine storage vesicles.Biochem. Pharmacol. 38, 2395–2404.

    Article  PubMed  CAS  Google Scholar 

  • Henry J.-P., Sagné C., Botton D., Isambert M.-F., and Gasnier B. (1997) Molecular pharmacology of the vesicular monoamine transporter.Adv. Pharmacol., in press.

  • Haubrich D. R., Wang P. F. L., Clody D. E., and Wedeking P. W. (1975) Increase in rat brain acetylcholine induced by choline or deanol.Life Sci. 17, 975–980.

    Article  PubMed  CAS  Google Scholar 

  • Howell M., Shirvan A., Stern-Bach Y., Steiner-Mordoch S., Strasser J. E., Dean G. E., and Schuldiner S. (1994) Cloning and functional expression of a tetrabenazine sensitive vesicular monoamine transporter from bovine chromaffin granules.FEBS Lett. 338, 16–22.

    Article  PubMed  CAS  Google Scholar 

  • Jahn R., Schiebler W., Ouimet C., and Greengard P. (1985) A 38,000 dalton membrane protein (p38) is present in synaptic vesicles.Proc. Natl. Acad. Sci. USA 82, 4137–4141.

    Article  PubMed  CAS  Google Scholar 

  • Jahn R. and Südhof T. C. (1993) Synaptic vesicle traffic: rush hour in the nerve terminal.J. Neurochem. 61, 12–21.

    Article  PubMed  CAS  Google Scholar 

  • Javitch J., D'amato R., Nye J., and Javitch J. (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity.Proc. Natl. Acad. Sci. USA 82, 2173–2177.

    Article  PubMed  CAS  Google Scholar 

  • Jenner P. and Olanow C. W. (1996) Oxidative stress and the pathogenesis of Parkinson's disease.Neurology 47 (6 Suppl. 3), S161-S170.

    PubMed  CAS  Google Scholar 

  • Johnson R. (1988) Accumulation of biological amines in chromaffin granules: a model for hormone and neurotransmitter transport.Physiol. Rev. 68, 232–307.

    PubMed  CAS  Google Scholar 

  • Kanner B. I. and Bendahan A. (1985) Transport of 5-hydroxytryptamine in membrane vesicles from rat basophilic leukemia cells.Biochim. Biophys. Acta 816, 403–410.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kelly R. B. (1993) Storage and release of neurotransmitters.Cell 72, 43–53.

    Article  PubMed  Google Scholar 

  • Kelly R. B. and Grote E. (1993) Protein targeting in the neuron.Ann. Rev. Neurosci. 16, 95–127.

    Article  PubMed  CAS  Google Scholar 

  • Kengaku M., Misawa H., and Deguchi T. (1993) Multiple mRNA species of choline acetyltransferase from rat spinal cord.Mol. Brain Res. 18, 71–76.

    Article  PubMed  CAS  Google Scholar 

  • Kish S. J., Distefano L. M., Dozic S., Robitaille Y., Rajput A., Deck J. H. N., and Hornykiewicz O. (1990)3H-vesamicol binding in human brain cholinergic deficiency disorders.Neurosci. Lett. 117, 347–352.

    Article  PubMed  CAS  Google Scholar 

  • Kitayama S., Shimada S., Xu H., Markham L., Donovan D. M., and Uhl G. R. (1992) Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding.Proc. Natl. Acad. Sci. USA 89, 7782–7785.

    Article  PubMed  CAS  Google Scholar 

  • Kleven M. S., Schuster C. R., and Seiden L. S. (1988) Effect of depletion of brain serotonine by repeated fenfluramine on neurochemical and anorectic effects of acute fenfluramine.J. Pharmacol. Exp. Therap. 246, 822–828.

    CAS  Google Scholar 

  • Knepper S. M., Grunewald G. L., and Rutledge C. O. (1988) Inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs.J. Pharmacol. Exp. Ther. 247, 487–494.

    PubMed  CAS  Google Scholar 

  • Knoth J., Zallakian M., and Njus D. (1981) Stoichiometry of H+-linked dopamine transport in chromaffin granule ghosts.Biochemistry 20, 6625–6629.

    Article  PubMed  CAS  Google Scholar 

  • Kölby L., Wängberg B., Ahlman H., Jansson S., Forssell-Aronsson E., Erickson J. D., and Nilsson O. (1997) Gastric carcinoid with histamine production, histamine transporter and expresion of somatostatin receptors.Digestion, in press.

  • Kornreich W. D. and Parsons S. M. (1988) Sidedness and chemical properties of the vesamicol receptor of cholinergic synaptic vesicles.Biochemistry 27, 5262–5267.

    Article  PubMed  CAS  Google Scholar 

  • Koshimura K., Miwa S., Lee K., Hayashi Y., Hasegawa H., Hamahata K., Fujiwara M., Kimura M., and Itokawa Y. (1990) Effects of choline administration on in vivo release and biosynthesis of acetylcholine in the rat striatum as studied by in vivo brain microdialysis.J. Neurochem. 54, 533–539.

    Article  PubMed  CAS  Google Scholar 

  • Krejci E., Gasnier B., Botton D., Isambert M.-F., Sagné C., Gagnon J., Massoulié J., and Henry J.-P. (1994) Expression and regulation of the bovine vesicular monoamine transporter gene.FEBS Lett. 335, 27–32.

    Article  Google Scholar 

  • Kuhl D. E., Minoshima S., Fessler J. A., Frey K. A., Foster N. L., Ficaro E. P., Wieland D. M., and Koeppe R. A. (1996) In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease.Ann. Neurol. 40, 399–410.

    Article  PubMed  CAS  Google Scholar 

  • Langston J. W., Ballard P., Tetrud J. W., and Irwin I. (1983) Chronic parkinsonism in humans due to a product of meperidine analog synthesis.Science 219, 979–980.

    Article  PubMed  CAS  Google Scholar 

  • Lehericy S., Brandel J.-P., Hirch E. C., Anglade P., Villares J., Scherman D., Duyckaerts C., Javoy-Agid F., and Agid Y. (1994) Monoamine vesicular uptake sites in patients with Parkinson's disease and Alzheimer's disease, as measured by titrated dihydrotetrabenazine autoradiography.Brain Res. 659, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Lesch K. P., Gross J., Wolozin B. L., Franzek E., Bengel D., Riederer P., and Murphy D. L. (1994) Direct sequencing of the reserpine-sensitive vesicular monoamine transporter complementary DNA in unipolar depression and manic depressive illness.Psychiatr. Genet. 4, 153–160.

    Article  PubMed  CAS  Google Scholar 

  • Linstedt A. D. and Kelly R. B. (1991a) Endocytosis of the synaptic vesicle protein, synaptophysin, requires the COOH-terminal tail.J. Physiol. (Paris) 85, 90–96.

    CAS  Google Scholar 

  • Linstedt A. D. and Kelly R. B. (1991b) Synaptophysin is sorted from endocytotic markers in neuroendocrine PC12 cells but not transfected fibroblasts.Neuron 7, 309–317.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Liu Y., Roghani A., and Edwards R. H. (1992b) Gene transfer of a reserpine-sensitive mechanism of resistance to MPP+.Proc. Natl. Acad. Sci. USA 89, 9074–9078.

    Article  PubMed  CAS  Google Scholar 

  • Liu Y., Schweitzer E., Nirenberg M. J., Pickel W. M., Evans C. J., and Edwards R. H. (1994) Preferential localization of a vesicular monoamine transporter to dense core vesicles in PC12 cells.J. Cell Biol. 127, 1419–1433.

    Article  PubMed  CAS  Google Scholar 

  • Lundberg J. M., Franco-Cereceda A., Lou Y. P., Modin A., and Pernow J. (1994) Differential release of classical transmitters and peptides, inMolecular and Cellular Mechanisms of Neurotransmitter Release (Stjarne L., Greengard P., Grillner S., Hokfelt T., and Ottoson D., eds.), Raven, New York, pp. 223–234.

    Google Scholar 

  • Mahata S. K., Mahata M., Fischer-Colbrie R., and Winkler H. (1993) Vesicle monoamine transporters 1 and 2: differential distribution and regulation of their mRNAs in chromaffin and ganglion cells of rat adrenal medulla.Neurosci. Lett. 156, 70–72.

    Article  PubMed  CAS  Google Scholar 

  • Maire J.-C. and Wurtman R. J. (1985) Effects of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat striatum.J. Physiol. (Paris) 80, 189–195.

    CAS  Google Scholar 

  • Mandel M. R. and Klerman G. L. (1978) Clinical use of antidepressants, stimulants, tricyclics and monoamine oxidase inhibitors, inPrinciples of Psychopharmacology, 2nd ed. (Clark W. G. and del Guidice J., eds.), Academic, New York, pp. 537–551.

    Google Scholar 

  • Marshall I. and Parsons S. (1987) The vesicular acetylcholine transport system.Trends Neurosci. 10, 174–177.

    Article  CAS  Google Scholar 

  • Matteoli M., Hainmann C., Torri-Tarelli F., Polak J. M., Ceccarelli B., and De Camilli P. (1988) Differential effect of α-latrotoxin on exocytosis from small synaptic vesicles and from large densecore vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction.Proc. Natl. Acad. Sci. USA 85, 7366–7370.

    Article  PubMed  CAS  Google Scholar 

  • Maycox P. R., Hell J. W., and Jahn R. (1990) Amino acid neurotransmission: spotlight on synaptic vesicles.Trends Neurosci. 13, 83–87.

    Article  PubMed  CAS  Google Scholar 

  • McMillen B. A., German D. C., and Shore P. A. (1980) Functional and pharmacological significance of brain dopamine and norepinephrine storage pools.Biochem. Pharmacol. 29, 3045–3050.

    Article  PubMed  CAS  Google Scholar 

  • Meltzer H. Y. and Stahl S. M. (1976) The dopamine hypothesis of schizophrenia: a review.Schizophr. Bull. 2, 19–76.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Merickel A., Rosandich P., Peter D., and Edwards R. H. (1995) Identification of residues involved in substrate recognition by a vesicular monoamine transporter.J. Biol. Chem. 270, 25,798–25,804.

    CAS  Google Scholar 

  • Misawa H., Shoji-Kasia Y., Takahashi R., Sugiyama T., Takagi H., Yoshida A., Yoshioka T., and Takahashi M. (1994) Storage and release of acetylcholine from PC12 cells expressing mouse choline acetyltransferase cDNA.Soc. Neurosci. Abstr. 20, 890.

    Google Scholar 

  • Misawa H., Takahashi R., and Deguchi T. (1995) Coordinate expression of vesicular acetylcholine transporter and choline acetyltransferase in sympathetic superior cervical neurones.NeuroReport 6, 965–968.

    Article  PubMed  CAS  Google Scholar 

  • Mundigl O. and De Camilli P. (1994) Formation of synaptic vesicles.Curr. Opin. Cell Biol. 6, 561–567.

    Article  PubMed  CAS  Google Scholar 

  • Navone F., Jahn R., Di Gioia G., Stukenbrok H., Greengard P., and De Camilli P. (1986) Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells.J. Cell Biol. 103, 2511–2527.

    Article  PubMed  CAS  Google Scholar 

  • Nirenberg M. J., Liu Y., Peter D., Edwards R. H., and Pickel V. M. (1995) The vesicular monoamine transporter 2 is present in small synaptic vesicles and preferentially localizes to large dense core vesicles in rat solitary tract nuclei.Proc. Natl. Acad. Sci. USA 92, 8773–8777.

    Article  PubMed  CAS  Google Scholar 

  • Nirenberg M. J., Chan J., Liu Y., Edwards R. H., and Pickel V. M. (1996) Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: potential sites for somatodendritic storage and release of dopamine.J. Neurosci. 16, 4135–4145.

    PubMed  CAS  Google Scholar 

  • Njus D., Kelley P. M., and Harnadek G. J. (1986) Bioenergetics of secretory vesicles.Biochim. Biophys. Acta 853, 237–265.

    PubMed  CAS  Google Scholar 

  • Nguyen M. L. and Parsons S. M. (1996) Interactions of protons with the acetylcholine transporter of synaptic vesicles.Prog. Brain Res. 109, 97–103.

    PubMed  CAS  Google Scholar 

  • Paxinos G. and Butcher L. L. (1985) Organizational principles of the brain as revealed by choline acetyltransferase and acetylcholinesterase distribution and projections, inThe Rat Nervous System vol. 1 (Paxinos G., ed.), Academic, New York, pp. 487–521.

    Google Scholar 

  • Parsons S. M., Prior C., and Marshall I. G. (1993) Acetylcholine transport, storage, and release.Int. Rev. Neurobiol. 35, 279–390.

    PubMed  CAS  Google Scholar 

  • Patrick R. L. and Kirshner N. (1971) Effect of stimulation on the levels of tyrosine hydroxylase, dopamine β-hydroxylase, and catecholamines in intact and denervated rat adrenal glands.Mol. Pharmacol. 7, 87–96.

    PubMed  CAS  Google Scholar 

  • Pepeu G., Casamenti G., Pepeu I. M., and Scali C. (1993) The brain cholinergic system in ageing mammals.J. Reprod. Fert., Suppl. 46, 155–162.

    CAS  Google Scholar 

  • Percisco A. M., Wang Q. W., Black D. W., Andreasen N. C., Uhl G. R., and Crowe R. R. (1996) Exclusion of close linkage between the synaptic vesicular monoamine transporter locus and schizophrenia spectrum disorders.Am. J. Med. Gen. 60, 563–565.

    Article  Google Scholar 

  • Perry E. K., Perry R. H., Blessed G., and Tomlinson B. E. (1977) Necropsy evidence of central cholinergic deficits in senile dementia.Lancet 1, 189.

    Article  PubMed  CAS  Google Scholar 

  • Perry E. K., Tomlinson B. E., Blessed G., Bergmann K., Gibson P. H., and Perry R. H. (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.Br. Med. J. 2, 1457–1459.

    PubMed  CAS  Google Scholar 

  • Peter D., Finn J. P., Klisak I., Liu Y., Kojis T., Heinzmann C., Roghani A., Sparkes R. S., and Edwards R. H. (1993) Chromosomal localization of the human vesicular amine transporter genes.Genomics 18, 720–723.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Peter D., Liu Y., Sternini C., de Giorgio R., Brecha N., and Edwards R. H. (1995) Differential expression of two vesicular monoamine transporters.J. Neurosci. 15, 6179–6188.

    PubMed  CAS  Google Scholar 

  • Peter D., Vu T., and Edwards R. H. (1996) Chimeric vesicular monoamine transporters identify structural domains that influence substrate affinity and sensitivity to tetrabenazine.J. Biol. Chem. 271, 2979–2986.

    Article  PubMed  CAS  Google Scholar 

  • Phillips J. H. (1982) Dynamic aspects of chromaffin granule structure.Neuroscience 7, 1595–1609.

    Article  PubMed  CAS  Google Scholar 

  • Philippu A. and Beyer J. (1973) Dopamine and noradrenaline transport into subcellular vesicles of the striatum.Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 387–402.

    Article  CAS  Google Scholar 

  • Ramsay R. R. and Singer T. P. (1986) Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria.J. Biol. Chem. 261, 7585–7587.

    PubMed  CAS  Google Scholar 

  • Reinhard J. F., Daniels A. J., and Viveros O. H. (1988) Potentiation by reserpine and tetrabenazine of brain catecholamine depletions by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the mouse; evidence for subcellular sequestration as basis for cellular resistance to the toxicant.Neurosci. Lett. 90, 349–353.

    Article  PubMed  CAS  Google Scholar 

  • Régnier-Vigouroux A., Tooze S. A., and Huttner W. B. (1991) Newly synthesized synaptophysin is transported to synaptic like microvesicles via constitutive secretory vesicles and the plasma membrane.EMBO. J. 10, 3589–3601.

    PubMed  Google Scholar 

  • Régnier-Vigouroux A. and Huttner W. B. (1993) Biogenesis of small synaptic vesicles and synaptic-like microvesicles.Neurochem. Res. 18, 59–64.

    Article  PubMed  Google Scholar 

  • Ricaurte G. A., Guillery R. W., Seiden L. S., Schuster C. R., and Moore R. Y. (1982) Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain.Brain Res. 235, 93–103.

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte G. A., Bryan G., Strauss L., Seiden L. S., and Schuster C. R. (1985) Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals.Science 229, 986–988.

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte G. A., DeLanney L. E., Irwin I., and Langston J. W. (1988) Toxic effect of MDMA on central serotonergic neurons in the primate: Importance of the route and frequency of drug administration.Brain Res. 446, 165–168.

    Article  PubMed  CAS  Google Scholar 

  • Roghani A., Feldman J., Kohan S. A., Shirzadi A., Gundersen C. B., Brecha N., and Edwards R. H. (1994) Molecular cloning of a putative vesicular transporter for acetylcholine.Proc. Natl. Acad. Sci. USA 91, 10,620–10,624.

    Article  CAS  Google Scholar 

  • Rossor M. N., Garret N. J., Johnson A. L., Mountjoy C. Q., Roth M., and Iversen L. L. (1982) A postmortem study of the cholinergic and GABA systems in senile dementia.Brain 105, 313–330.

    Article  PubMed  CAS  Google Scholar 

  • Ruberg M., Mayo W., Brice A., Duyckaerts C., Hauw J. J., Simon H., LeMoal M., and Agid Y. (1990) Choline acetyltransferase activity and [3H]vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions.Neuroscience 35, 327–333.

    Article  PubMed  CAS  Google Scholar 

  • Rudnick G. (1986) ATP-driven H+ pumping into intracellular organelles.Ann. Rev. Physiol. 48, 403–413.

    CAS  Google Scholar 

  • Rudnick G., Steiner-Mordoch S. S., Fishkes H., Stern-Bach Y., and Schuldiner S. (1990) Energetics of reserpine binding and occlusion by the chromaffin granule transporter.Biochemistry 29, 603–608.

    Article  PubMed  CAS  Google Scholar 

  • Rudnick G. and Wall S. C. (1992) The molecular mechanism of ‘ecstasy’ [3,4-methylenedioxymethamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release.Proc. Natl. Acad. Sci. USA 89, 1817–1821.

    Article  PubMed  CAS  Google Scholar 

  • Sagné C., Isambert M.-F., Vanderckhove J., Henry J.-P., and Gasnier B. (1997) The photoactivable inhibitor 7-azido-8-iodoketanserin labels the N terminus of the vesicular monoamine transporter from bovine chromaffin granules.Biochemistry 36, 3345–352.

    Article  PubMed  Google Scholar 

  • Schäfer M. K.-H., Weihe E., Varoqui H., Eiden L. E., and Erickson J. D. (1994) Distribution of the vesicular acetylcholine transporter (VAChT) in the central and peripheral nervous systems of the rat.J. Mol. Neurosci. 5, 1–18.

    Article  PubMed  Google Scholar 

  • Schäfer M. K.-H., Weihe E., Erickson J. D., and Eiden L. E. (1995) Human and monkey cholinergic neurons visualized in paraffin-embedded tissues by immunoreactivity for VAChT, the vesicular acetylcholine transporter.J. Mol. Neurosci. 6, 225–235.

    Article  PubMed  Google Scholar 

  • Schäfer M. K.-H., Schütz B., Erickson J. D., Eiden L. E., and Weihe E. (1996) Visualization of vesicular monoamine and acetylcholine transporters in developing neurons and neuroendocrine cells.Soc. Neurosci. Abstr. 22, 29.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Scherman D. and Henry J.-P. (1984) Reserpine binding to bovine chromaffin granule membranes. Characterization and comparison with dihydrotetrabenazine binding.Mol. Pharmacol. 25, 113–122.

    PubMed  CAS  Google Scholar 

  • Scherman D. and Boschi G. (1988) Time required for transmitter accumulation inside monoaminergic storage vesicles differs in peripheral and in central systems.Neuroscience 27, 1029–1035.

    Article  PubMed  CAS  Google Scholar 

  • Schubert D. and Klier F. G. (1977) Storage and release of acetylcholine by a clonal cell line.Proc. Natl. Acad. Sci. USA 74, 5184–5188.

    Article  PubMed  CAS  Google Scholar 

  • Schuldiner S., Steiner-Mordoch S., Yelin R., Wall S. C., and Rudnick G. (1993a) Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters.Mol. Pharmacol. 44, 1227–1231.

    PubMed  CAS  Google Scholar 

  • Schuldiner S., Liu Y., and Edwards R. H. (1993b) Reserpine binding to a vesicular amine transporter expressed in chinese hamster ovary fibroblasts.J. Biol. Chem. 268, 29–34.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Shirvan A., Laskar O., Steiner-Mordoch S., and Schuldiner S. (1994) Histidine-419 plays a role in energy coupling in the vesicular monoamine transporter from rat.FEBS Lett. 356, 145–150.

    Article  PubMed  CAS  Google Scholar 

  • Seiden L. S. and Sabol K. E. (1996) Methamphetamine and methylenedioxymethamphetamine neurotoxicity: possible mechanisms of cell destruction.NIDA Res. Monogr. 163, 251–276.

    PubMed  CAS  Google Scholar 

  • Sietzen M., Schober M., Fischer-Colbrie R., Scherman D., Sperk G., and Winkler H. (1987) Rat adrenal medulla: levels of chromogranins, enkephalins, dopamine β-hydroxylase and of the amine transporter are changed by nervous activity and hypophysectomy.Neuroscience 22, 131–139.

    Article  PubMed  CAS  Google Scholar 

  • Sievert M. K. and Ruoho A. E. (1996) Identification of drug binding sites on the synaptic vesicle monoamine translocator.FASEB J. 10, A1233 (abstract #1350).

    Google Scholar 

  • Silva N. L. and Bunney B. S. (1988) Intracellular studies of dopamine neurons in vitro: pacemakers modulated by dopamine.Eur. J. Pharmacol. 149, 307–315.

    Article  PubMed  CAS  Google Scholar 

  • Slotkin T. A., Nemeroff C. B., Bissette G., and Seidler F. J. (1994) Overexpression of the high affinity choline transporter in cortical regions affected by Alzheimer's disease.J. Clin. Invest. 94, 696–702.

    PubMed  CAS  Google Scholar 

  • Song H.-J., Ming G.-L., Fon E., Bellocchio E., Edwards R. H., and Poo M.-M. (1997) Expression of a putative vesicular acetylcholine transporter facilitates quantal transmitter packaging.Neuron 18, 815–826.

    Article  PubMed  CAS  Google Scholar 

  • Stachowiak M. K., Hong J. S., and Viveros O. H. (1990) Coordinate and differential regulation of phenylethanolamine N-methyltransferase, tyrosine hydroxylase and proenkephalin mRNAs by neural and hormonal mechanisms in cultured bovine adrenal medullary cells.Brain Res. 510, 277–288.

    Article  PubMed  CAS  Google Scholar 

  • Steiner-Mordoch S., Shirvan A., and Schuldiner S. (1996) Modification of the pH profile and tetrabenazine sensitivity of rat VMAT1 by replacement of aspartate 404 with glutamate.J. Biol. Chem. 271, 13,048–13,054.

    Article  CAS  Google Scholar 

  • Strada O., Vyas S., Hirsch E. C., Rugerg M., Brice A., Agid Y., and Jovoy-Agid F. (1992) Decreased choline acetyltransferase mRNA expression in the nucleus basalis of Meynert in Alzheimer disease: An in situ hybridization study.Proc. Natl. Acad. Sci. USA 89, 9549–9553.

    Article  PubMed  CAS  Google Scholar 

  • Strader C. D., Sigal C. D., Candelore M. R., Rands E., Hill W. S., and Dixon R. A. F. (1988) Conserved aspartic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function.J. Biol. Chem. 263, 10,267–10,271.

    CAS  Google Scholar 

  • Strader C. D., Candelore M. R., Hill W. S., Sigal I. S., and Dixon R. A. F. (1989) Identification of two serine residues involved in agonist activation of the β-adrenergic receptor.J. Biol. Chem. 264, 13,572–13,578.

    CAS  Google Scholar 

  • Sulston J., Dew M., and Brenner S. (1975) Dopaminergic neurons in the nematodeCaenorhabditis elegans.J. Comp. Neur. 163, 215–226.

    Article  PubMed  CAS  Google Scholar 

  • Sulzer D. and Rayport S. (1990) Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action.Neuron 5, 797–808.

    Article  PubMed  CAS  Google Scholar 

  • Surratt C. K., Persico A. M., Yang X.-D., Edgar S. R., Bird G. S., Hawkins A. L., Griffin C. A., Li X., Jabs E. W., and Uhl G. A. (1993) A human synaptic vesicle monoamine transporter cDNA predicts postranslational modifications, reveals chromosome 10 gene localization and identifiesTaqI RFLPs.FEBS Lett. 318, 325–330.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi N., Miner L. L., Sora I., Ujike I., Revay R. S., Kostic V., Jackson-Lewis V., Przedborski S., and Uhl G. R. (1997) VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion and enhanced MPTP toxicity.Proc. Natl. Acad. Sci. USA 94, 9938–9943.

    Article  PubMed  CAS  Google Scholar 

  • Takimoto G. S., Stittworth J. D., Bianchi B. R., and Stephens J. K. (1983) Differential sensitivity of hypothalamus norepinephrine and striatal dopamine to catecholamine depleting agents.J. Pharmacol. Exp. Ther. 226, 432–439.

    PubMed  CAS  Google Scholar 

  • Tanner V. A., Ploug T., and Tao-Cheng J.-H. (1996) Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures.J. Histochem. Cytochem. 44, 1481–1488.

    PubMed  CAS  Google Scholar 

  • Thureson-Klein A. K., Klein R. L., Zhu P.-C., and Kong J.-Y. (1988) Differential release of transmitters and neuropeptides co-stored in central and peripheral neurons, inCellular and Molecular Basis of Synaptic Transmission (Zimmermann H., ed.), Springer-Verlag, Berlin, pp. 137–151.

    Google Scholar 

  • Thoenen H., Mueller R. A., and Axelrod J. (1969) An enzymatic assay for octopamine and other β-hydroxylated phenylethylamines.J. Pharmacol. Exp. Ther. 160, 249–253.

    Google Scholar 

  • Thoenen H. (1974) Trans-synaptic enzyme inductionLife Sci. 14, 223–235.

    Article  PubMed  CAS  Google Scholar 

  • Tian X., Sun X., and Suszkiw J. B. (1996) Developmental age-dependent upregulation of choline acetyltransferase and vesicular acetylcholine transporter mRNA expression in neonatal rat septum by nerve growth factor.Neurosci. Lett. 201, 134–136.

    Article  Google Scholar 

  • Ulus I., Wurtman R. J., Mauron C., and Blusztajn J. K. (1989) Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum.Brain Res. 484, 217–227.

    Article  PubMed  CAS  Google Scholar 

  • Unsicker K., Hofman H. D., Höhne I., Müller T. H., and Schmidt R. (1983) Phenotypic plasticity of cultured bovine chromaffin cells. II. Fiber outgrowth induced by elevated potassium: morphology and ionic requirements.Dev. Brain Res. 9, 369–379.

    Article  CAS  Google Scholar 

  • Usdin T. B., Eiden L. E., Bonner T. I., and Erickson J. D. (1995) Molecular biology of the vesicular ACh transporter.TINS 18, 218–224.

    PubMed  CAS  Google Scholar 

  • van Praag H. M. (1978) Amine hypothesis of affective disorders, inHandbook of Psychopharmacology, vol. 13, (Iversen L. L., Iversen S. D., and Snyder S. H., eds.), Plenum, New York, pp. 187–297.

    Google Scholar 

  • Varoqui H., Diebler M.-F., Meunier F-.M., Rand J. B., Usdin T. B., Bonner T. I., Eiden L. E., and Erickson J. D. (1994) Cloning and expression of the vesamicol binding protein from the marine rayTorpedo. Homology with the putative vesicular acetylcholine transporter UNC-17 fromCaenorhabditis elegans.FEBS Lett. 342, 97–102.

    Article  PubMed  CAS  Google Scholar 

  • Varoqui H., Meunier F.-M., Meunier F. A., Molgo J., Berrard S., Cervini R., Mallet J., Israel M., and Diebler M.-F. (1996) Expression of the vesicular acetylcholine transporter in mammalian cells.Prog. Brain Res. 109, 83–95.

    PubMed  CAS  Google Scholar 

  • Varoqui H. and Erickson J. D. (1996a) Active transport of acetylcholine by the human vesicular acetylcholine transporter.J. Biol. Chem. 271, 27,229–27,232.

    CAS  Google Scholar 

  • Varoqui H. and Erickson J. D. (1996b) Targeting of the human vesicular monoamine and acetylcholine transporters to secretory organelles in rat PC-12 cells.Soc. Neurosci. Abstr. 22, 149.

    Google Scholar 

  • Varoqui H. and Erickson J. D. (1997) Vesicular transporter chimeras identify domains important for acetylcholine transport and targeting to synaptic vesicles.Soc. Neurosci. Abst., in press.

  • Weaver J. H. and Dupree J. D. (1982) Conditions required for reserpine binding to the catecholamine transporter on chromaffin granule ghosts.Eur. J. Pharmacol. 80, 437–438.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Weihe E., Tao-Cheng J.-H., Schäfer M. K.-H., Erickson J. D., and Eiden L. E. (1996) 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.

    Article  PubMed  CAS  Google Scholar 

  • Weiner N. (1985) Norepinephrine, epinephrine, and the sympathomimetic amines, inThe Pharmacological Basis of Therapeutics (Gilman A. G., Goodman L. S., and Gilman A., eds.), MacMillan, New York, pp. 138–175.

    Google Scholar 

  • West A. E., Provoda C., Neve R. L., and Buckley K. M. (1997) Protein targeting in neurons and endocrine cells.Adv. Pharmacol, in press.

  • Whitehouse P. J., Price D. L., Clark A. W., Coyle J. T., and DeLong M. R. (1981) Alzheimer disease: evidence for a selective loss of cholinergic neurons in the nucleus basalis.Ann. Neurol. 10, 122–126.

    Article  PubMed  CAS  Google Scholar 

  • Wilson J. M., Levey A. I., Rajput A., Ang L., Guttman M., Shannak K., Niznik H. B., Hornykiewicz O., Pifl C., and Kish S. J. (1996) Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson's disease.Neurology 47, 718–726.

    PubMed  CAS  Google Scholar 

  • Wurtman R. J. (1992) Choline metabolism as a basis for the selective vulnerability of cholinergic neurons.TINS 15, 117–122.

    PubMed  CAS  Google Scholar 

  • Yamaguchi A., Akasaka T., Ono N., Someya Y., Nakatani M., and Sawai T. (1992a) Metal-tetracycline/H+ antiporter ofEscherichia coli encoded by transposon Tn10: roles of the aspartyl residues located in the putative transmembrane helices.J. Biol. Chem. 267, 7490–7498.

    PubMed  CAS  Google Scholar 

  • Yamaguchi A., Ono N., Akasaka T., and Sawai T. (1992b) Serine residues responsible for tetracycline transport are on a vertical stripe including asp-84 on one side of transmembrane helix 3 in transposon Tn10-encoded tetracycline/H+ antiporter ofEscherichia coli.FEBS Lett. 307, 229–232.

    Article  PubMed  CAS  Google Scholar 

  • Yelin R. and Schuldiner S. (1995) The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters.FEBS Lett. 377, 201–207.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroscience Center and Department of Pharmacology, Louisiana State University Medical Center, 2020 Gravier Street, Suite D, 70112, New Orleans, LA

    Hélène Varoqui & Jeffrey D. Erickson

Authors
  1. Hélène Varoqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey D. Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey D. Erickson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Varoqui, H., Erickson, J.D. Vesicular neurotransmitter transporters. Mol Neurobiol 15, 165–191 (1997). https://doi.org/10.1007/BF02740633

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02740633

Index Entries

Search

Navigation