Skip to main content
SpringerLink
Log in

Recognition of Psychostimulants, Antidepressants, and Other Inhibitors of Synaptic Neurotransmitter Uptake by the Plasma Membrane Monoamine Transporters

  • Chapter
Drug Addiction

  • 2258 Accesses

Abstract

The plasma membrane monoamine transporters terminate neurotransmission by removing dopamine, norepinephrine, or serotonin from the synaptic cleft between neurons. Specific inhibitors for these transporters, including the abused psychostimulants cocaine and amphetamine and the tricyclic and SSRI classes of antidepressants, exert their physiological effects by interfering with synaptic uptake and thus prolonging the actions of the monoamine. Pharmacological, biochemical, and immunological characterization of the many site-directed, chimeric, and deletion mutants generated for the plasma membrane monoamine transporters have revealed much about the commonalities and dissimilarities between transporter substrate, ion, and inhibitor binding sites. Mutations that alter the binding affinity or substrate uptake inhibition potency of inhibitors by at least 3-fold are the focus of this review. These findings are clarifying the picture regarding substrate uptake inhibitor/transporter protein interactions at the level of the drug pharmacophore and the amino acid residue, information necessary for rational design of novel medications for substance abuse and a variety of psychiatric disorders.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bannon MJ. The dopamine transporter: role in neurotoxicity and human disease. Toxicol Appl Pharmacol. 2005;204:355-360.

    PubMed  CAS  Google Scholar 

  2. Rothman RB, Baumann MH. Monoamine transporters and psychostimulant drugs. Eur J Pharmacol. 2003;479:23-40.

    PubMed  CAS  Google Scholar 

  3. Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ. Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet. 1999;354:2132-2133.

    PubMed  CAS  Google Scholar 

  4. Spencer TJ, Biederman J, Madras BK, et al. In vivo neuroreceptor imaging in attention-deficit/ hyperactivity disorder: a focus on the dopamine transporter. Biol Psychiatry. 2005;57: 1293-1300.

    PubMed  CAS  Google Scholar 

  5. Eriksen JL, Dawson TM, Dickson DW, Petrucelli L. Caught in the act: alpha-synuclein is the culprit in Parkinson’s disease. Neuron. 2003;40:453-456.

    PubMed  CAS  Google Scholar 

  6. Sidhu A, Wersinger C, Vernier P. Alpha-synuclein regulation of the dopaminergic trans-porter: a possible role in the pathogenesis of Parkinson’s disease. FEBS Lett. 2004;565:1-5.

    PubMed  CAS  Google Scholar 

  7. Dubertret C, Hanoun N, Ades J, Hamon M, Gorwood P. Family-based association study of the 5-HT transporter gene and schizophrenia. Int J Neuropsychopharmacol. 2005;8:87-92.

    PubMed  CAS  Google Scholar 

  8. Keikhaee MR, Fadai F, Sargolzaee MR, Javanbakht A, Najmabadi H, Ohadi M. Association analysis of the dopamine transporter (DAT1)-67A/T polymorphism in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2005;135:47-49.

    Google Scholar 

  9. Wong DF, Harris JC, Naidu S, et al. Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo. Proc Natl Acad Sci USA. 1996;93:5539-5543.

    PubMed  CAS  Google Scholar 

  10. Hahn MK, Robertson D, Blakely RD. A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters. J Neurosci. 2003;23:4470-4478.

    PubMed  CAS  Google Scholar 

  11. Maron E, Kuikka JT, Shlik J, Vasar V, Vanninen E, Tiihonen J. Reduced brain serotonin transporter binding in patients with panic disorder. Psychiatry Res. 2004;132:173-181.

    PubMed  CAS  Google Scholar 

  12. Sutcliffe JS, Delahanty RJ, Prasad HC, et al. Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet. 2005;77:265-279.

    PubMed  CAS  Google Scholar 

  13. Caspi A, Sugden K, Moffitt TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386-389.

    PubMed  CAS  Google Scholar 

  14. Inoue K, Itoh K, Yoshida K, Shimizu T, Suzuki T. Positive association between T-182C poly-morphism in the norepinephrine transporter gene and susceptibility to major depressive dis-order in a Japanese population. Neuropsychobiology. 2004;50:301-304.

    PubMed  CAS  Google Scholar 

  15. Saier MH Jr. A functional-phylogenetic system for the classification of transport proteins. J Cell Biochem. 1999;75:84-94.

    Google Scholar 

  16. Rudnick G. Mechanisms of biogenic amine neurotransmitter transporters. In: Reith MEA, ed. Neurotransmitter Transporters: Structure, Function, and Regulation. Totowa, NJ: Humana Press Inc; 1997:73-100.

    Google Scholar 

  17. Goldberg NR, Beuming T, Soyer OS, Goldstein RA, Weinstein H, Javitch JA. Probing con-formational changes in neurotransmitter transporters: a structural context. Eur J Pharmacol. 2003;479:3-12.

    PubMed  CAS  Google Scholar 

  18. Chen N, Zhen J, Reith ME. Mutation of Trp84 and Asp313 of the dopamine transporter reveals similar mode of binding interaction for GBR12909 and benztropine as opposed to cocaine. J Neurochem. 2004;89:853-864.

    PubMed  CAS  Google Scholar 

  19. Kitayama S, Shimada S, Xu H, Markham L, Donovan DM, Uhl GR. Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc Natl Acad Sci USA. 1992;89:7782-7785.

    PubMed  CAS  Google Scholar 

  20. Strader CD, Sigal IS, Candelore MR, Rands E, Hill WS, Dixon RAF. Conserved aspartic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function. J Biol Chem. 1988;263:10267-10271.

    PubMed  CAS  Google Scholar 

  21. Wang W, Sonders MS, Ukairo OT, Scott H, Kloetzel MK, Surratt CK. Dissociation of high-affinity cocaine analog binding and dopamine uptake inhibition at the dopamine transporter. Mol Pharmacol. 2003;64:430-439.

    PubMed  CAS  Google Scholar 

  22. Ukairo OT, Bondi CD, Newman AH, et al. Recognition of benztropine by the dopamine transporter (DAT) differs from that of the classical dopamine uptake inhibitors cocaine, meth-ylphenidate and mazindol as a function of a DAT transmembrane 1 aspartic acid residue. J Pharmacol Exp Ther. 2005;314:575-583.

    PubMed  CAS  Google Scholar 

  23. Barker EL, Moore KR, Rakhshan F, Blakely RD. Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J Neurosci. 1999;19: 4705-4717.

    PubMed  CAS  Google Scholar 

  24. Carroll FI, Lewin AH, Boja JW, Kuhar MJ. Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter. J Med Chem. 1992;35:969-981.

    PubMed  CAS  Google Scholar 

  25. Madras BK, Pristupa ZB, Niznik HB, et al. Nitrogen-based drugs are not essential for block-ade of monoamine transporters. Synapse. 1996;24:340-348.

    PubMed  CAS  Google Scholar 

  26. Kozikowski AP, Simoni D, Roberti M, et al. Synthesis of 8-oxa analogues of norcocaine endowed with interesting cocaine-like activity. Bioorg Med Chem Lett. 1999;9:1831-1836.

    PubMed  CAS  Google Scholar 

  27. Chen N, Vaughan RA, Reith ME. The role of conserved tryptophan and acidic residues in the human dopamine transporter as characterized by site-directed mutagenesis. J Neurochem. 2001;77:1116-1127.

    PubMed  CAS  Google Scholar 

  28. Zhen J, Maiti S, Chen N, Dutta AK, Reith ME. Interaction between a hydroxypiperidine ana-logue of 4-(2-benzhydryloxy-ethyl)-1-(4-fluorobenzyl)piperidine and aspartate 68 in the human dopamine transporter. Eur J Pharmacol. 2004;506:17-26.

    PubMed  CAS  Google Scholar 

  29. Lin Z, Wang W, Uhl GR. Dopamine transporter tryptophan mutants highlight candidate dopamine- and cocaine-selective domains. Mol Pharmacol. 2000;58:1581-1592.

    PubMed  CAS  Google Scholar 

  30. Reith ME, Berfield JL, Wang LC, Ferrer JV, Javitch JA. The uptake inhibitors cocaine and benztropine differentially alter the conformation of the human dopamine transporter. J Biol Chem. 2001;276:29012-29018.

    PubMed  CAS  Google Scholar 

  31. Adkins EM, Barker EL, Blakely RD. Interactions of tryptamine derivatives with serotonin transporter species variants implicate transmembrane domain I in substrate recognition. Mol Pharmacol. 2001;59:514-523.

    PubMed  CAS  Google Scholar 

  32. Barker EL, Perlman MA, Adkins EM, et al. High affinity recognition of serotonin transporter antagonists defined by species-scanning mutagenesis. J Biol Chem. 1998;273:19459-19468.

    PubMed  CAS  Google Scholar 

  33. Javitch JA, Shi L, Liapakis G. Use of the substituted cysteine accessibility method to study the structure and function of G protein-coupled receptors. Methods Enzymol. 2002;343:137-156.

    PubMed  Google Scholar 

  34. Henry LK, Adkins EM, Han Q, Blakely RD. Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane domain I. J Biol Chem. 2003;278:37052-37063.

    PubMed  CAS  Google Scholar 

  35. Ferrer JV, Javitch JA. Cocaine alters the accessibility of endogenous cysteines in putative extracellular and intracellular loops of the human dopamine transporter. Proc Natl Acad Sci USA. 1998;95:9238-9243.

    PubMed  CAS  Google Scholar 

  36. Gaffaney JD, Vaughan RA. Uptake inhibitors but not substrates induce protease resistance in extracellular loop two of the dopamine transporter. Mol Pharmacol. 2004;65:692-701.

    PubMed  CAS  Google Scholar 

  37. Lin Z, Wang W, Kopajtic T, Revay RS, Uhl GR. Dopamine transporter: transmembrane phe-nylalanine mutations can selectively influence dopamine uptake and cocaine analog recogni-tion. Mol Pharmacol. 1999;56:434-447.

    PubMed  CAS  Google Scholar 

  38. Melamed N, Kanner BI. Transmembrane domains I and II of the gamma-aminobutyric acid transporter GAT-4 contain molecular determinants of substrate specificity. Mol Pharmacol. 2004;65:1452-1461.

    PubMed  CAS  Google Scholar 

  39. Zhou Y, Bennett ER, Kanner BI. The aqueous accessibility in the external half of transmem-brane domain I of the GABA transporter GAT-1 is modulated by its ligands. J Biol Chem. 2004;279:13800-13808.

    PubMed  CAS  Google Scholar 

  40. Wu X, Gu HH. Cocaine affinity decreased by mutations of aromatic residue phenylalanine 105 in the transmembrane domain 2 of dopamine transporter. Mol Pharmacol. 2003;63:653-658.

    PubMed  CAS  Google Scholar 

  41. Sato Y, Zhang YW, Androutsellis-Theotokis A, Rudnick G. Analysis of transmembrane domain 2 of rat serotonin transporter by cysteine scanning mutagenesis. J Biol Chem. 2004;279:22926-22933.

    PubMed  CAS  Google Scholar 

  42. Chen R, Han DD, Gu HH. A triple mutation in the second transmembrane domain of mouse dopamine transporter markedly decreases sensitivity to cocaine and methylphenidate. J Neurochem. 2005;94:352-359.

    PubMed  CAS  Google Scholar 

  43. Sucic S, Paczkowski FA, Runkel F, Bonisch H, Bryan-Lluka LJ. Functional significance of a highly conserved glutamate residue of the human noradrenaline transporter. J Neurochem. 2002;81:344-354.

    PubMed  CAS  Google Scholar 

  44. Keshet GI, Bendahan A, Su H, Mager S, Lester HA, Kanner BI. Glutamate-101 is critical for the function of the sodium and chloride-coupled GABA transporter GAT-1. FEBS Lett. 1995;371:39-42.

    PubMed  CAS  Google Scholar 

  45. Lee SH, Kang SS, Son H, Lee YS. The region of dopamine transporter encompassing the 3rd transmembrane domain is crucial for function. Biochem Biophys Res Commun. 1998;246: 347-352.

    PubMed  CAS  Google Scholar 

  46. Lee SH, Chang MY, Lee KH, Park BS, Lee YS, Chin HR. Importance of valine at position 152 for the substrate transport and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane bind-ing of dopamine transporter. Mol Pharmacol. 2000;57:883-889.

    PubMed  CAS  Google Scholar 

  47. Lin Z, Uhl GR. Dopamine transporter mutants with cocaine resistance and normal dopamine uptake provide targets for cocaine antagonism. Mol Pharmacol. 2002;61:885-891.

    PubMed  CAS  Google Scholar 

  48. Chen J-G, Sachpatzidis A, Rudnick G. The third transmembrane domain of the serotonin transporter contains residues associated with substrate and cocaine binding. J Biol Chem. 1997;272:28321-28327.

    PubMed  CAS  Google Scholar 

  49. Chen J-G, Rudnick G. Permeation and gating residues in serotonin transporter. Proc Natl Acad Sci USA. 2000;97:1044-1049.

    PubMed  CAS  Google Scholar 

  50. Loland CJ, Granas C, Javitch JA, Gether U. Identification of intracellular residues in the dopamine transporter critical for regulation of transporter conformation and cocaine binding. J Biol Chem. 2004;279:3228-3238.

    PubMed  CAS  Google Scholar 

  51. Kristensen AS, Larsen MB, Johnsen LB, Wiborg O. Mutational scanning of the human serot-onin transporter reveals fast translocating serotonin transporter mutants. Eur J Neurosci. 2004;19:1513-1523.

    PubMed  Google Scholar 

  52. Mortensen OV, Kristensen AS, Wiborg O. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants. J Neurochem. 2001;79:237-247.

    PubMed  CAS  Google Scholar 

  53. Chen F, Larsen MB, Neubauer HA, Sanchez C, Plenge P, Wiborg O. Characterization of an allosteric citalopram-binding site at the serotonin transporter. J Neurochem. 2005;92:21-28.

    PubMed  CAS  Google Scholar 

  54. Paczkowski FA, Bryan-Lluka LJ. Tyrosine residue 271 of the norepinephrine transporter is an important determinant of its pharmacology. Brain Res Mol Brain Res. 2001;97:32-42.

    PubMed  CAS  Google Scholar 

  55. Kopajtic T, Rucker C, Seidleck BK, Blaschak CJ, Surratt CK. Glycine substitution of selected dopamine transporter (DAT) proline residues predicted for transmembrane domains: effects on dopamine uptake and affinities for cocaine analogs and other DAT ligands. Soc Neurosci Abs. 1997;23:408.

    Google Scholar 

  56. Lin Z, Itokawa M, Uhl GR. Dopamine transporter proline mutations influence dopamine uptake, cocaine analog recognition, and expression. FASEB J. 2000;14:715-728.

    PubMed  CAS  Google Scholar 

  57. Paczkowski FA, Bryan-Lluka LJ. Role of proline residues in the expression and function of the human noradrenaline transporter. J Neurochem. 2004;88:203-211.

    Article  PubMed  CAS  Google Scholar 

  58. Williams KA, Deber CM. Proline residues in transmembrane helices: structural or dynamic role? Biochemistry. 1991;30:8919-8923.

    PubMed  CAS  Google Scholar 

  59. Brandl CJ, Deber CM. Hypothesis about the function of membrane-buried proline residues in transport proteins. Proc Natl Acad Sci USA. 1986;83:917-921.

    PubMed  CAS  Google Scholar 

  60. Barlow DJ, Thornton JM. Helix geometry in proteins. J Mol Biol. 1988;201:601-619.

    PubMed  CAS  Google Scholar 

  61. Li S-C, Goto NK, Williams KA, Deber CM. α-Helical, but not β-sheet, propensity of proline is determined by peptide environment. Proc Natl Acad Sci USA. 1996;93:6676-6681.

    PubMed  CAS  Google Scholar 

  62. Ri Y, Ballesteros JA, Abrams CK, et al. The role of a conserved proline residue in mediating conformational changes associated with voltage gating of Cx32 gap junctions. Biophys J. 1999;76:2887-2898.

    PubMed  CAS  Google Scholar 

  63. Visiers I, Weinstein H, Rudnick G, Stephan MM. A second site rescue mutation partially restores functional expression to the serotonin transporter mutant V382P. Biochemistry. 2003;42:6784-6793.

    PubMed  CAS  Google Scholar 

  64. Sansom MS, Weinstein H. Hinges, swivels and switches: the role of prolines in signalling via transmembrane alpha-helices. Trends Pharmacol Sci. 2000;21:445-451.

    PubMed  CAS  Google Scholar 

  65. Eisenman G, Dani JA. An introduction to molecular architecture and permeability of ion channels. Annu Rev Biophys Biophys Chem. 1987;16:205-226.

    PubMed  CAS  Google Scholar 

  66. Sansom MSP. Proline residues in transmembrane helices of channel and transport proteins: a molecular modelling study. Protein Eng. 1992;5:53-60.

    PubMed  CAS  Google Scholar 

  67. Chen N, Sun L, Reith ME. Cationic interactions at the human dopamine transporter reveal binding conformations for dopamine distinguishable from those for the cocaine analog 2 alpha-carbomethoxy-3 alpha-(4-fluorophenyl)tropane. J Neurochem. 2002;81:1383-1393.

    PubMed  CAS  Google Scholar 

  68. Chen N, Reith ME. Na+ and the substrate permeation pathway in dopamine transporters. Eur J Pharmacol. 2003;479:213-221.

    PubMed  CAS  Google Scholar 

  69. Buck KJ, Amara SG. Structural domains of catecholamine transporter chimeras involved in selective inhibition by antidepressants and psychomotor stimulants. Mol Pharmacol. 1995;48: 1030-1037.

    PubMed  CAS  Google Scholar 

  70. Giros B, Wang Y, Suter S, Mestikawy SE, Pifl C, Caron MG. Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. J Biol Chem. 1994;269:15985-15988.

    PubMed  CAS  Google Scholar 

  71. Roubert C, Cox PJ, Bruss M, Hamon M, Bonisch H, Giros B. Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity. J Biol Chem. 2001;276:8254-8260.

    PubMed  CAS  Google Scholar 

  72. Strader CD, Candelore MR, Hill WS, Sigal IS, Dixon RA. Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor. J Biol Chem. 1989;264: 13572-13578.

    PubMed  CAS  Google Scholar 

  73. Danek Burgess KS, Justice JB Jr. Effects of serine mutations in transmembrane domain 7 of the human norepinephrine transporter on substrate binding and transport. J Neurochem. 1999;73:656-664.

    PubMed  CAS  Google Scholar 

  74. Penado KM, Rudnick G, Stephan MM. Critical amino acid residues in transmembrane span 7 of the serotonin transporter identified by random mutagenesis. J Biol Chem. 1998;273: 28098-28106.

    PubMed  CAS  Google Scholar 

  75. Kamdar G, Penado KM, Rudnick G, Stephan MM. Functional role of critical stripe residues in transmembrane span 7 of the serotonin transporter: effects of Na+, Li+, and methanethio-sulfonate reagents. J Biol Chem. 2001;276:4038-4045.

    PubMed  CAS  Google Scholar 

  76. Itokawa M, Lin Z, Cai NS, et al. Dopamine transporter transmembrane domain polar mutants: ΔG and ΔΔG values implicate regions important for transporter functions. Mol Pharmacol. 2000;57:1093-1103.

    PubMed  CAS  Google Scholar 

  77. Uhl GR, Lin Z. The top 20 dopamine transporter mutants: structure-function relationships and cocaine actions. Eur J Pharmacol. 2003;479:71-82.

    PubMed  CAS  Google Scholar 

  78. Sur C, Betz H, Schloss P. A single serine residue controls the cation dependence of substrate transport by the rat serotonin transporter. Proc Natl Acad Sci USA. 1997;94:7639-7644.

    PubMed  CAS  Google Scholar 

  79. Barker EL, Kimmel HL, Blakely RD. Chimeric human and rat serotonin transporters reveal domains involved in recognition of transporter ligands. Mol Pharmacol. 1994;46:799-807.

    PubMed  CAS  Google Scholar 

  80. Barker EL, Blakely RD. Identification of a single amino acid, Phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter. Mol Pharmacol. 1996;50:957-965.

    PubMed  CAS  Google Scholar 

  81. Smicun Y, Campbell SD, Chen MA, Gu H, Rudnick G. The role of external loop regions in serotonin transport: loop scanning mutagenesis of the serotonin transporter external domain. J Biol Chem. 1999;274:36058-36064.

    PubMed  CAS  Google Scholar 

  82. Norgaard-Nielsen K, Norregaard L, Hastrup H, Javitch JA, Gether U. Zn(2+) site engineering at the oligomeric interface of the dopamine transporter. FEBS Lett. 2002;524:87-91.

    PubMed  CAS  Google Scholar 

  83. Loland CJ, Norregaard L, Gether U. Defining proximity relationships in the tertiary structure of the dopamine transporter: identification of a conserved glutamic acid as a third coordinate in the endogenous Zn(2+)-binding site. J Biol Chem. 1999;274:36928-36934.

    PubMed  CAS  Google Scholar 

  84. Fischer JF, Cho AK. Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model. J Pharmacol Exp Ther. 1979;208:203-209.

    PubMed  CAS  Google Scholar 

  85. Khoshbouei H, Sen N, Guptaroy B, et al. N-terminal phosphorylation of the dopamine trans-porter is required for amphetamine-induced efflux. PLoS Biol. 2004;2:E78.

    PubMed  Google Scholar 

  86. Granas C, Ferrer J, Loland CJ, Javitch JA, Gether U. N-terminal truncation of the dopamine transporter abolishes phorbol ester- and substance P receptor-stimulated phosphorylation without impairing transporter internalization. J Biol Chem. 2003;278:4990-5000.

    PubMed  Google Scholar 

  87. Seidel S, Singer EA, Just H, et al. Amphetamines take two to tango: an oligomer-based coun-ter-transport model of neurotransmitter transport explores the amphetamine action. Mol Pharmacol. 2005;67:140-151.

    PubMed  CAS  Google Scholar 

  88. Sucic S, Bryan-Lluka LJ. The role of the conserved GXXXRXG motif in the expression and function of the human norepinephrine transporter. Brain Res Mol Brain Res. 2002;108:40-50.

    PubMed  CAS  Google Scholar 

  89. Loland CJ, Norregaard L, Litman T, Gether U. Generation of an activating Zn(2+) switch in the dopamine transporter: mutation of an intracellular tyrosine constitutively alters the con-formational equilibrium of the transport cycle. Proc Natl Acad Sci USA. 2002;99:1683-1688.

    PubMed  CAS  Google Scholar 

  90. Chen N, Rickey J, Berfield JL, Reith ME. Aspartate 345 of the dopamine transporter is criti-cal for conformational changes in substrate translocation and cocaine binding. J Biol Chem. 2004;279:5508-5519.

    PubMed  CAS  Google Scholar 

  91. Lee FJ, Pristupa ZB, Ciliax BJ, Levey AI, Niznik HB. The dopamine transporter carboxyl-ter-minal tail: truncation/substitution mutants selectively confer high affinity dopamine uptake while attenuating recognition of the ligand binding domain. J Biol Chem. 1996;271:20885-20894.

    PubMed  CAS  Google Scholar 

  92. Hastrup H, Karlin A, Javitch JA. Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane seg-ment. Proc Natl Acad Sci USA. 2001;98:10055-10060.

    PubMed  CAS  Google Scholar 

  93. Hastrup H, Sen N, Javitch JA. The human dopamine transporter forms a tetramer in the plasma membrane: cross-linking of a cysteine in the fourth transmembrane segment is sensi-tive to cocaine analogs. J Biol Chem. 2003;278:45045-45048.

    PubMed  CAS  Google Scholar 

  94. Kilic F, Rudnick G. Oligomerization of serotonin transporter and its functional conse-quences. Proc Natl Acad Sci USA. 2000;97:3106-3111.

    PubMed  CAS  Google Scholar 

  95. Torres GE, Yao WD, Mohn AR, et al. Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001;30:121-134.

    PubMed  CAS  Google Scholar 

  96. Lee KH, Kim MY, Kim DH, Lee YS. Syntaxin 1A and receptor for activated C kinase inter-act with the N-terminal region of human dopamine transporter. Neurochem Res. 2004;29: 1405-1409.

    PubMed  CAS  Google Scholar 

  97. Sung U, Apparsundaram S, Galli A, et al. A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity. J Neurosci. 2003;23:1697-1709.

    PubMed  CAS  Google Scholar 

  98. Deken SL, Beckman ML, Boos L, Quick MW. Transport rates of GABA transporters: regu-lation by the N-terminal domain and syntaxin 1A. Nat Neurosci. 2000;3:998-1003.

    PubMed  CAS  Google Scholar 

  99. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB. Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994;45:125-135.

    PubMed  CAS  Google Scholar 

  100. Eshleman AJ, Carmolli M, Cumbay M, Martens CR, Neve KA, Janowsky A. Characteristics of drug interactions with recombinant biogenic amine transporters expressed in the same cell type. J Pharmacol Exp Ther. 1999;289:877-885.

    PubMed  CAS  Google Scholar 

  101. Williams KA, Geldmacher-Kaufer U, Padan E, Schuldiner S, Kuhlbrandt W. Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 A resolution. EMBO J. 1999;18:3558-3563.

    PubMed  CAS  Google Scholar 

  102. Williams KA. Three-dimensional structure of the ion-coupled transport protein NhaA. Nature. 2000;403:112-115.

    PubMed  CAS  Google Scholar 

  103. Ravna AW, Sylte I, Dahl SG. Molecular model of the neural dopamine transporter. J Comput Aided Mol Des. 2003;17:367-382.

    PubMed  CAS  Google Scholar 

  104. Ravna AW, Sylte I, Dahl SG. Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters. J Pharmacol Exp Ther. 2003;307:34-41.

    PubMed  CAS  Google Scholar 

  105. Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E. Crystal structure of a bacterial homo-logue of Na+/Cl−-dependent neurotransmitter transporters. Nature. 2005;437:215-223.

    PubMed  CAS  Google Scholar 

  106. Lee SH, Chang MY, Jeon DJ, et al. The functional domains of dopamine transporter for cocaine analog, CFT binding. Exp Mol Med. 2002;34:90-94.

    PubMed  CAS  Google Scholar 

  107. Vaughan RA. Photoaffinity-labeled ligand binding domains on dopamine transporters identi-fied by peptide mapping. Mol Pharmacol. 1995;47:956-964.

    PubMed  CAS  Google Scholar 

  108. Vaughan RA, Kuhar MJ. Dopamine transporter ligand binding domains: structural and functional properties revealed by limited proteolysis. J Biol Chem. 1996;271:21672-21680.

    PubMed  CAS  Google Scholar 

  109. Vaughan RA, Agoston GE, Lever JR, Newman AH. Differential binding of tropane-based photoaffinity ligands on the dopamine transporter. J Neurosci. 1999;19:630-636.

    PubMed  CAS  Google Scholar 

  110. Lever JR, Zou MF, Parnas ML, et al. Radioiodinated azide and isothiocyanate derivatives of cocaine for irreversible labeling of dopamine transporters: synthesis and covalent binding studies. Bioconjug Chem. 2005;16:644-649.

    PubMed  CAS  Google Scholar 

  111. Vaughan RA, Parnas ML, Gaffaney JD, et al. Affinity labeling the dopamine transporter lig-and binding site. J Neurosci Methods. 2005;143:33-40.

    PubMed  CAS  Google Scholar 

  112. Wirtz SE, Parnas L, Jackson TV, et al. Identification of an MFZ 2-24 photoaffinity labeling site on the human dopamine transporter. Soc Neurosci Abstr. 2004;33:53-19.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282

    Christopher K. Surratt, Okechukwu T. Ukairo & Suneetha Ramanujapuram

Authors
  1. Christopher K. Surratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Okechukwu T. Ukairo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suneetha Ramanujapuram
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher K. Surratt .

Editor information

Editors and Affiliations

  1. National Institute on Drug Abuse, Bethesda, MD, USA

    Rao S. Rapaka

  2. College of Medicine and Public Health, Ohio State University, Columbus, OH, USA

    Wolfgang Sadée

Rights and permissions

Reprints and permissions

Copyright information

© 2008 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Surratt, C.K., Ukairo, O.T., Ramanujapuram, S. (2008). Recognition of Psychostimulants, Antidepressants, and Other Inhibitors of Synaptic Neurotransmitter Uptake by the Plasma Membrane Monoamine Transporters. In: Rapaka, R.S., Sadée, W. (eds) Drug Addiction. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76678-2_18

Download citation

Publish with us

Policies and ethics

Societies and partnerships

Search

Navigation