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Molecular Neurobiology

, Volume 15, Issue 2, pp 165–191 | Cite as

Vesicular neurotransmitter transporters

Potential sites for the regulation of synaptic function
  • Hélène Varoqui
  • Jeffrey D. Erickson
Original Articles

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.

Index Entries

VMAT1 VMAT2 VAChT vesicular monoamine transporter vesicular acetylcholine transporter cholinergic gene locus gene knockout large dense core vesicles small synaptic vesicles targeting neurotoxicity neurodegeneration Parkinson's disease Alzheimer's disease 

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References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. Amara S. and Kuhar M. J. (1992) Neurotransmitter transporters—recent progress.Ann. Rev. Neurosci. 16, 73–93.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. Asher S. W. and Aminoff M. J. (1981) Tetrabenazine and movement disorders.Neurology 31, 1051–1054.PubMedGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. Axelrod J. (1971) Noradrenaline: fate and control of its biosynthesis.Science 173, 598–606.PubMedCrossRefGoogle Scholar
  9. Bahr B. A. and Parsons S. M. (1986) Acetylcholine transport and drug inhibition kinetics inTorpedo synaptic vesicles.J. Neurochem. 46, 1214–1218.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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
  13. Ben-Shachar D., Zuk R., and Glinka Y. (1995) Dopamine neurotoxicity: inhibition of mitochondrial respiration.J. Neurochem. 64, 718–723.PubMedCrossRefGoogle Scholar
  14. Bennett M. K. and Scheller R. H. (1994) A molecular description of synaptic vesicle membrane trafficking.Ann. Rev. Biochem. 63, 63–100.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.Google Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. Blusztajn J. K. and Wurtman R. J. (1983) Choline and cholinergic neurons.Science 221, 614–619.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. Brenner S. (1974) The genetics of Caenorhabditis elegans.Genetics 77, 71–94.PubMedGoogle Scholar
  21. Buu N. T. (1989) Modification of vesicular dopamine and norepinephrine by monoamine oxidase inhibitors.Biochem. Pharmacol. 38, 1685–1692.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.Google Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. Cohen E. L. and Wurtman R. J. (1975) Brain acetylcholine: increase after systemic choline administration.Life Sci. 16, 1095–1102.PubMedCrossRefGoogle Scholar
  28. Costa D. and Sandler M., eds. (1972)Monoamine Oxidases—New Vistas. Advances in Biochemical Psychopharmacology, vol. 5, Raven, New York.Google Scholar
  29. 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.PubMedGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. Davies P. and Maloney A. J. P. (1976) Selective loss of cholinergic neurons in Alzheimer's disease.Lancet 2, 1403.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.Google Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.Google Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.PubMedGoogle Scholar
  49. Erickson, J. D. (1997) A chimeric vesicular monoamine transporter dissociates sensitivity to tetrabenazine and unsubstituted aromatic amines.Adv. Pharmacol., in press.Google Scholar
  50. Fahn S. and Cohen G. (1992) The oxidant stress hypothesis in Parkinson's disease: evidence supporting it.Ann. Neurol. 32, 804–812.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. 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.PubMedCrossRefGoogle Scholar
  53. 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.CrossRefGoogle Scholar
  54. Gasnier B., Scherman D., and Henry J.-P. (1985) Dicyclohexylcarbodiimide inhibits the monoamine carrier of bovine chromaffin granule membrane.Biochemistry 24, 1239–1244.PubMedCrossRefGoogle Scholar
  55. 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.PubMedCrossRefGoogle Scholar
  56. 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
  57. Green L. A. and Rein G. (1977a) Synthesis, storage, and release of acetylcholine by a noradrenergic pheochromocytoma cell line.Nature 268, 349–351.CrossRefGoogle Scholar
  58. 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.CrossRefGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. Geula C. and Mesulam M. M. (1989) Cortical cholinergic fibers in ageing and Alzheimer's disease: a morphometric study.Neuroscience 33, 469–476.PubMedCrossRefGoogle Scholar
  61. 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.PubMedCrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 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.PubMedCrossRefGoogle Scholar
  64. 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.Google Scholar
  65. 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.PubMedCrossRefGoogle Scholar
  66. 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.PubMedCrossRefGoogle Scholar
  67. 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.PubMedCrossRefGoogle Scholar
  68. Jahn R. and Südhof T. C. (1993) Synaptic vesicle traffic: rush hour in the nerve terminal.J. Neurochem. 61, 12–21.PubMedCrossRefGoogle Scholar
  69. 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.PubMedCrossRefGoogle Scholar
  70. Jenner P. and Olanow C. W. (1996) Oxidative stress and the pathogenesis of Parkinson's disease.Neurology 47 (6 Suppl. 3), S161-S170.PubMedGoogle Scholar
  71. Johnson R. (1988) Accumulation of biological amines in chromaffin granules: a model for hormone and neurotransmitter transport.Physiol. Rev. 68, 232–307.PubMedGoogle Scholar
  72. 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.PubMedCrossRefGoogle Scholar
  73. Kanner B. I. and Schuldiner S. (1987) Mechanism of transport and storage of neurotransmitters.CRC Crit. Rev. Biochem. 22, 1–38.PubMedGoogle Scholar
  74. Kelly R. B. (1993) Storage and release of neurotransmitters.Cell 72, 43–53.PubMedCrossRefGoogle Scholar
  75. Kelly R. B. and Grote E. (1993) Protein targeting in the neuron.Ann. Rev. Neurosci. 16, 95–127.PubMedCrossRefGoogle Scholar
  76. Kengaku M., Misawa H., and Deguchi T. (1993) Multiple mRNA species of choline acetyltransferase from rat spinal cord.Mol. Brain Res. 18, 71–76.PubMedCrossRefGoogle Scholar
  77. 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.PubMedCrossRefGoogle Scholar
  78. 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.PubMedCrossRefGoogle Scholar
  79. 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.Google Scholar
  80. 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.PubMedGoogle Scholar
  81. Knoth J., Zallakian M., and Njus D. (1981) Stoichiometry of H+-linked dopamine transport in chromaffin granule ghosts.Biochemistry 20, 6625–6629.PubMedCrossRefGoogle Scholar
  82. 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.Google Scholar
  83. Kornreich W. D. and Parsons S. M. (1988) Sidedness and chemical properties of the vesamicol receptor of cholinergic synaptic vesicles.Biochemistry 27, 5262–5267.PubMedCrossRefGoogle Scholar
  84. 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.PubMedCrossRefGoogle Scholar
  85. 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.CrossRefGoogle Scholar
  86. 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.PubMedCrossRefGoogle Scholar
  87. 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.PubMedCrossRefGoogle Scholar
  88. 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.PubMedCrossRefGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.Google Scholar
  91. 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.PubMedCrossRefGoogle Scholar
  92. 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.PubMedCrossRefGoogle Scholar
  93. 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.PubMedCrossRefGoogle Scholar
  94. 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.PubMedCrossRefGoogle Scholar
  95. 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
  96. 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.PubMedCrossRefGoogle Scholar
  97. 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.Google Scholar
  98. 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
  99. Marshall I. and Parsons S. (1987) The vesicular acetylcholine transport system.Trends Neurosci. 10, 174–177.CrossRefGoogle Scholar
  100. 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.PubMedCrossRefGoogle Scholar
  101. Maycox P. R., Hell J. W., and Jahn R. (1990) Amino acid neurotransmission: spotlight on synaptic vesicles.Trends Neurosci. 13, 83–87.PubMedCrossRefGoogle Scholar
  102. 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.PubMedCrossRefGoogle Scholar
  103. Meltzer H. Y. and Stahl S. M. (1976) The dopamine hypothesis of schizophrenia: a review.Schizophr. Bull. 2, 19–76.PubMedGoogle Scholar
  104. Merickel A. and Edwards R. H. (1995) Transport of histamine by vesicular monoamine transporter-2.Neuropharmacology 34, 1543–1547.PubMedCrossRefGoogle Scholar
  105. 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.Google Scholar
  106. 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
  107. 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.PubMedCrossRefGoogle Scholar
  108. Mundigl O. and De Camilli P. (1994) Formation of synaptic vesicles.Curr. Opin. Cell Biol. 6, 561–567.PubMedCrossRefGoogle Scholar
  109. 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.PubMedCrossRefGoogle Scholar
  110. 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.PubMedCrossRefGoogle Scholar
  111. 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.PubMedGoogle Scholar
  112. Njus D., Kelley P. M., and Harnadek G. J. (1986) Bioenergetics of secretory vesicles.Biochim. Biophys. Acta 853, 237–265.PubMedGoogle Scholar
  113. Nguyen M. L. and Parsons S. M. (1996) Interactions of protons with the acetylcholine transporter of synaptic vesicles.Prog. Brain Res. 109, 97–103.PubMedGoogle Scholar
  114. 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
  115. Parsons S. M., Prior C., and Marshall I. G. (1993) Acetylcholine transport, storage, and release.Int. Rev. Neurobiol. 35, 279–390.PubMedGoogle Scholar
  116. 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.PubMedGoogle Scholar
  117. 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.Google Scholar
  118. 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.CrossRefGoogle Scholar
  119. 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.PubMedCrossRefGoogle Scholar
  120. 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.PubMedGoogle Scholar
  121. 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.PubMedCrossRefGoogle Scholar
  122. 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.PubMedGoogle Scholar
  123. 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.PubMedGoogle Scholar
  124. 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.PubMedCrossRefGoogle Scholar
  125. Phillips J. H. (1982) Dynamic aspects of chromaffin granule structure.Neuroscience 7, 1595–1609.PubMedCrossRefGoogle Scholar
  126. Philippu A. and Beyer J. (1973) Dopamine and noradrenaline transport into subcellular vesicles of the striatum.Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 387–402.CrossRefGoogle Scholar
  127. 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.PubMedGoogle Scholar
  128. 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.PubMedCrossRefGoogle Scholar
  129. 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.PubMedGoogle Scholar
  130. Régnier-Vigouroux A. and Huttner W. B. (1993) Biogenesis of small synaptic vesicles and synaptic-like microvesicles.Neurochem. Res. 18, 59–64.PubMedCrossRefGoogle Scholar
  131. 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.PubMedCrossRefGoogle Scholar
  132. 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.PubMedCrossRefGoogle Scholar
  133. 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.PubMedCrossRefGoogle Scholar
  134. 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.CrossRefGoogle Scholar
  135. 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.PubMedCrossRefGoogle Scholar
  136. 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.PubMedCrossRefGoogle Scholar
  137. Rudnick G. (1986) ATP-driven H+ pumping into intracellular organelles.Ann. Rev. Physiol. 48, 403–413.Google Scholar
  138. 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.PubMedCrossRefGoogle Scholar
  139. 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.PubMedCrossRefGoogle Scholar
  140. 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.PubMedCrossRefGoogle Scholar
  141. 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.PubMedCrossRefGoogle Scholar
  142. 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.PubMedCrossRefGoogle Scholar
  143. 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
  144. 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.PubMedCrossRefGoogle Scholar
  145. 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.PubMedGoogle Scholar
  146. 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.PubMedCrossRefGoogle Scholar
  147. 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.PubMedCrossRefGoogle Scholar
  148. 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.PubMedGoogle Scholar
  149. 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.PubMedGoogle Scholar
  150. Schuldiner S., Shirvan A., and Linial M. (1995) Vesicular neurotransmitter transporters: from bacteria to humans.Physiol. Rev. 75, 369–392.PubMedGoogle Scholar
  151. 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.PubMedCrossRefGoogle Scholar
  152. Seiden L. S. and Sabol K. E. (1996) Methamphetamine and methylenedioxymethamphetamine neurotoxicity: possible mechanisms of cell destruction.NIDA Res. Monogr. 163, 251–276.PubMedGoogle Scholar
  153. 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.PubMedCrossRefGoogle Scholar
  154. 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
  155. 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.PubMedCrossRefGoogle Scholar
  156. 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.PubMedGoogle Scholar
  157. 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.PubMedCrossRefGoogle Scholar
  158. 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.PubMedCrossRefGoogle Scholar
  159. 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.CrossRefGoogle Scholar
  160. 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.PubMedCrossRefGoogle Scholar
  161. 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.Google Scholar
  162. 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.Google Scholar
  163. Sulston J., Dew M., and Brenner S. (1975) Dopaminergic neurons in the nematodeCaenorhabditis elegans.J. Comp. Neur. 163, 215–226.PubMedCrossRefGoogle Scholar
  164. 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.PubMedCrossRefGoogle Scholar
  165. 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.PubMedCrossRefGoogle Scholar
  166. 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.PubMedCrossRefGoogle Scholar
  167. 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.PubMedGoogle Scholar
  168. 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.PubMedGoogle Scholar
  169. 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
  170. 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
  171. Thoenen H. (1974) Trans-synaptic enzyme inductionLife Sci. 14, 223–235.PubMedCrossRefGoogle Scholar
  172. 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.CrossRefGoogle Scholar
  173. 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.PubMedCrossRefGoogle Scholar
  174. 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.CrossRefGoogle Scholar
  175. 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.PubMedGoogle Scholar
  176. 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
  177. 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.PubMedCrossRefGoogle Scholar
  178. 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.PubMedGoogle Scholar
  179. 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.Google Scholar
  180. 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
  181. 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.Google Scholar
  182. 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.PubMedCrossRefGoogle Scholar
  183. 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.PubMedCrossRefGoogle Scholar
  184. 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.PubMedCrossRefGoogle Scholar
  185. 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
  186. West A. E., Provoda C., Neve R. L., and Buckley K. M. (1997) Protein targeting in neurons and endocrine cells.Adv. Pharmacol, in press.Google Scholar
  187. 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.PubMedCrossRefGoogle Scholar
  188. 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.PubMedGoogle Scholar
  189. Wurtman R. J. (1992) Choline metabolism as a basis for the selective vulnerability of cholinergic neurons.TINS 15, 117–122.PubMedGoogle Scholar
  190. 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.PubMedGoogle Scholar
  191. 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.PubMedCrossRefGoogle Scholar
  192. Yelin R. and Schuldiner S. (1995) The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters.FEBS Lett. 377, 201–207.PubMedCrossRefGoogle Scholar

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© Humana Press Inc 1997

Authors and Affiliations

  1. 1.Neuroscience Center and Department of PharmacologyLouisiana State University Medical CenterNew Orleans

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