Organic Cation Transporters (OCTs) as Modulators of Behavior and Mood

  • Alejandro Orrico
  • Sophie GautronEmail author


The organic cation transporters (OCTs) fulfill important functions in the absorption and excretion of endogenous compounds and xenobiotics in peripheral organs, which have been well documented. Two OCT subtypes, OCT2 and OCT3, are also expressed in the brain and predominant in aminergic projection regions. The last decade has seen substantial advances in our understanding of the implication of these transporters in a range of integrated functions of the central nervous system. Various approaches exploiting pharmacological inhibitors and mutant mice models for OCTs have disclosed that they are involved in particular in behaviors related to osmoregulation, anxiety, stress, antidepressant action and addiction. We summarize in this chapter recent developments on the roles of OCTs in central nervous system, focusing on mood-related behaviors.


Organic cation transporter Brain Osmoregulation Anxiety Stress Antidepressants Addiction 





Decynium 22




Dopamine transporter


Forced-swim test




Norepinephrine transporter


Organic cation transporter


Serotonin transporter


Subfornical organ


Tail suspension test



Financial support was provided the Agence Nationale de la Recherche (ANR-13-SAMENTA-0003-01).


  1. 1.
    Koepsell H, Schmitt BM, Gorboulev V. Organic cation transporters. Rev Physiol Biochem Pharmacol. 2003;150:36–90.PubMedGoogle Scholar
  2. 2.
    Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res. 2007;24(7):1227–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Breidert T, Spitzenberger F, Grundemann D, Schomig E. Catecholamine transport by the organic cation transporter type 1 (OCT1). Br J Pharmacol. 1998;125(1):218–24.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, et al. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998;54(2):342–52.PubMedGoogle Scholar
  5. 5.
    Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, et al. Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998;273(47):30915–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Grundemann D, Schechinger B, Rappold GA, Schomig E. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998;1(5):349–51.PubMedCrossRefGoogle Scholar
  7. 7.
    Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E. Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999;56(1):1–10.PubMedGoogle Scholar
  8. 8.
    Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, et al. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998;273(49):32776–86.PubMedCrossRefGoogle Scholar
  9. 9.
    Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13–25.PubMedCrossRefGoogle Scholar
  10. 10.
    Zwart R, Verhaagh S, Buitelaar M, Popp-Snijders C, Barlow DP. Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice. Mol Cell Biol. 2001;21(13):4188–96.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Jonker JW, Wagenaar E, Mol CA, Buitelaar M, Koepsell H, Smit JW, et al. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Mol Cell Biol. 2001;21(16):5471–7.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Jonker JW, Wagenaar E, Van Eijl S, Schinkel AH. Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations. Mol Cell Biol. 2003;23(21):7902–8.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Iversen LL. The uptake of catecholamines at high perfusion concentrations in the rat isolated heart: a novel catechol amine uptake process. Br J Pharmacol. 1965;25:18–33.Google Scholar
  14. 14.
    Bonisch H. Extraneuronal transport of catecholamines. Pharmacology. 1980;21(2):93–108.PubMedCrossRefGoogle Scholar
  15. 15.
    Graefe K-H, Bonisch H. The transport of amines across the axonal membranes of noradrenergic and dopaminergic neurons. In: Trendelenburg U, Weiner N, editors. Handbook of experimental pharmacology. Berlin: Springer-Verlag; 1988.Google Scholar
  16. 16.
    Russ H, Sonna J, Keppler K, Baunach S, Schomig E. Cyanine-related compounds: a novel class of potent inhibitors of extraneuronal noradrenaline transport. Naunyn Schmiedebergs Arch Pharmacol. 1993;348(5):458–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Russ H, Staust K, Martel F, Gliese M, Schomig E. The extraneuronal transporter for monoamine transmitters exists in cells derived from human central nervous system glia. Eur J Neurosci. 1996;8(6):1256–64.PubMedCrossRefGoogle Scholar
  18. 18.
    Grundemann D, Babin-Ebell J, Martel F, Ording N, Schmidt A, Schomig E. Primary structure and functional expression of the apical organic cation transporter from kidney epithelial LLC-PK1 cells. J Biol Chem. 1997;272(16):10408–13.PubMedCrossRefGoogle Scholar
  19. 19.
    Hayer-Zillgen M, Bruss M, Bonisch H. Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002;136(6):829–36.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, et al. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997;16(7):871–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, et al. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem. 1998;273(26):15971–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Haag C, Berkels R, Grundemann D, Lazar A, Taubert D, Schomig E. The localisation of the extraneuronal monoamine transporter (EMT) in rat brain. J Neurochem. 2004;88(2):291–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Vialou V, Amphoux A, Zwart R, Giros B, Gautron S. Organic cation transporter 3 (Slc22a3) is implicated in salt-intake regulation. J Neurosci. 2004;24(11):2846–51.PubMedCrossRefGoogle Scholar
  24. 24.
    Vialou V, Balasse L, Callebert J, Launay JM, Giros B, Gautron S. Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice. J Neurochem. 2008;106(3):1471–82.PubMedGoogle Scholar
  25. 25.
    Bacq A, Balasse L, Biala G, Guiard B, Gardier AM, Schinkel A, et al. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry. 2012;17(9):926–39.PubMedCrossRefGoogle Scholar
  26. 26.
    Couroussé T, Bacq A, Belzung C, Guiard B, Balasse L, Louis F, et al. Brain organic cation transporter 2 controls response and vulnerability to stress and GSK3β signaling. Mol Psychiatry. 2015;20(7):889–900.PubMedCrossRefGoogle Scholar
  27. 27.
    Daws LC, Montanez S, Owens WA, Gould GG, Frazer A, Toney GM, et al. Transport mechanisms governing serotonin clearance in vivo revealed by high-speed chronoamperometry. J Neurosci Methods. 2005;143(1):49–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, et al. Organic cation transporter 3: keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A. 2008;105(48):18976–81.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Gasser PJ, Lowry CA, Orchinik M. Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: potential role for organic cation transporter 3 in stress-induced modulation of monoaminergic neurotransmission. J Neurosci. 2006;26(34):8758–66.PubMedCrossRefGoogle Scholar
  30. 30.
    Feng N, Lowry CA, Lukkes JL, Orchinik M, Forster GL, Renner KJ. Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint. Brain Res. 2010;1326:105–13.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Nakayama H, Kitaichi K, Ito Y, Hashimoto K, Takagi K, Yokoi T, et al. The role of organic cation transporter-3 in methamphetamine disposition and its behavioral response in rats. Brain Res. 2007;1184:260–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Kitaichi K, Fukuda M, Nakayama H, Aoyama N, Ito Y, Fujimoto Y, et al. Behavioral changes following antisense oligonucleotide-induced reduction of organic cation transporter-3 in mice. Neurosci Lett. 2005;382(1–2):195–200.PubMedCrossRefGoogle Scholar
  33. 33.
    Cui M, Aras R, Christian WV, Rappold PM, Hatwar M, Panza J, et al. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci U S A. 2009;106(19):8043–8.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Bunin MA, Wightman RM. Quantitative evaluation of 5-hydroxytryptamine (serotonin) neuronal release and uptake: an investigation of extrasynaptic transmission. J Neurosci. 1998;18(13):4854–60.PubMedGoogle Scholar
  35. 35.
    Mundorf ML, Joseph JD, Austin CM, Caron MG, Wightman RM. Catecholamine release and uptake in the mouse prefrontal cortex. J Neurochem. 2001;79(1):130–42.PubMedCrossRefGoogle Scholar
  36. 36.
    Mitchell K, Oke AF, Adams RN. In vivo dynamics of norepinephrine release-reuptake in multiple terminal field regions of rat brain. J Neurochem. 1994;63(3):917–26.PubMedCrossRefGoogle Scholar
  37. 37.
    Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG. Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci U S A. 1998;95(7):4029–34.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Bengel D, Murphy DL, Andrews AM, Wichems CH, Feltner D, Heils A, et al. Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine (“Ecstasy”) in serotonin transporter-deficient mice. Mol Pharmacol. 1998;53(4):649–55.PubMedGoogle Scholar
  39. 39.
    Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW, et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci. 2000;3(5):465–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Gasser PJ, Orchinik M, Raju I, Lowry CA. Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain. J Comp Neurol. 2009;512(4):529–55.PubMedCrossRefGoogle Scholar
  41. 41.
    Osborn JW, Hendel MD, Collister JP, Ariza-Guzman PA, Fink GD. The role of the subfornical organ in angiotensin II-salt hypertension in the rat. Exp Physiol. 2012;97(1):80–8.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Zhang B, Li M, Wang L, Li C, Lou Y, Liu J, et al. The association between the polymorphisms in a sodium channel gene SCN7A and essential hypertension: a case-control study in the northern Han Chinese. Ann Hum Genet. 2015;79(1):28–36.Google Scholar
  43. 43.
    Wultsch T, Grimberg G, Schmitt A, Painsipp E, Wetzstein H, Breitenkamp AF, et al. Decreased anxiety in mice lacking the organic cation transporter 3. J Neural Transm. 2009;116(6):689–97.PubMedCrossRefGoogle Scholar
  44. 44.
    Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol. 2003;70(2):83–244.PubMedCrossRefGoogle Scholar
  45. 45.
    Murphy DL, Moya PR, Fox MA, Rubenstein LM, Wendland JR, Timpano KR. Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity. Philos Trans R Soc Lond B Biol Sci. 2013;368(1615):20120435.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Lazar A, Walitza S, Jetter A, Gerlach M, Warnke A, Herpertz-Dahlmann B, et al. Novel mutations of the extraneuronal monoamine transporter gene in children and adolescents with obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2008;11(1):35–48.PubMedCrossRefGoogle Scholar
  47. 47.
    Fontenelle LF, Mendlowicz MV, Versiani M. The descriptive epidemiology of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(3):327–37.PubMedCrossRefGoogle Scholar
  48. 48.
    Zhang L, Schaner ME, Giacomini KM. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998;286(1):354–61.PubMedGoogle Scholar
  49. 49.
    Gorboulev V, Shatskaya N, Volk C, Koepsell H. Subtype-specific affinity for corticosterone of rat organic cation transporters rOCT1 and rOCT2 depends on three amino acids within the substrate binding region. Mol Pharmacol. 2005;67(5):1612–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, et al. Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol. 2003;24(3):151–80.PubMedCrossRefGoogle Scholar
  51. 51.
    Ulrich-Lai YM, Herman JP. Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci. 2009;10(6):397–409.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Mazure CM, Bruce ML, Maciejewski PK, Jacobs SC. Adverse life events and cognitive-personality characteristics in the prediction of major depression and antidepressant response. Am J Psychiatry. 2000;157(6):896–903.PubMedCrossRefGoogle Scholar
  53. 53.
    Lupien SJ, McEwen BS, Gunnar MR, Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci. 2009;10(6):434–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Surget A, Saxe M, Leman S, Ibarguen-Vargas Y, Chalon S, Griebel G, et al. Drug-dependent requirement of hippocampal neurogenesis in a model of depression and of antidepressant reversal. Biol Psychiatry. 2008;64(4):293–301.PubMedCrossRefGoogle Scholar
  55. 55.
    Gourley SL, Wu FJ, Kiraly DD, Ploski JE, Kedves AT, Duman RS, et al. Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression. Biol Psychiatry. 2008;63(4):353–9.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Karege F, Perroud N, Burkhardt S, Schwald M, Ballmann E, La Harpe R, et al. Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims. Biol Psychiatry. 2007;61(2):240–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Polter A, Beurel E, Yang S, Garner R, Song L, Miller CA, et al. Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. Neuropsychopharmacology. 2010;35(8):1761–74.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto T, et al. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002;300(3):918–24.PubMedCrossRefGoogle Scholar
  59. 59.
    Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005;20(5):379–86.PubMedCrossRefGoogle Scholar
  60. 60.
    Baganz N, Horton R, Martin K, Holmes A, Daws LC. Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun. J Neurosci. 2010;30(45):15185–95.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    de Kloet ER, Joels M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 2005;6(6):463–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry. 1998;59 Suppl 14:11–4.PubMedGoogle Scholar
  63. 63.
    Porsolt RD, Brossard G, Hautbois C, Roux S. Rodent models of depression: forced swimming and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci. 2001;Chapter 8:Unit 8.10A.Google Scholar
  64. 64.
    Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005;29(4–5):571–625.PubMedCrossRefGoogle Scholar
  65. 65.
    Rahman Z, Ring RH, Young K, Platt B, Lin Q, Schechter LE, et al. Inhibition of uptake 2 (or extraneuronal monoamine transporter) by normetanephrine potentiates the neurochemical effects of venlafaxine. Brain Res. 2008;1203:68–78.PubMedCrossRefGoogle Scholar
  66. 66.
    Horton RE, Apple DM, Owens WA, Baganz NL, Cano S, Mitchell NC, et al. Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression. J Neurosci. 2013;33(25):10534–43.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    David DJ, Samuels BA, Rainer Q, Wang JW, Marsteller D, Mendez I, et al. Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron. 2009;62(4):479–93.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Surget A, Tanti A, Leonardo ED, Laugeray A, Rainer Q, Touma C, et al. Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry. 2011;16(12):1177–88.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Beique J, de Montigny C, Blier P, Debonnel G. Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000;39(10):1800–12.PubMedCrossRefGoogle Scholar
  70. 70.
    Yanpallewar SU, Fernandes K, Marathe SV, Vadodaria KC, Jhaveri D, Rommelfanger K, et al. Alpha2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. J Neurosci. 2010;30(3):1096–109.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Szabo ST, Blier P. Effects of the selective norepinephrine reuptake inhibitor reboxetine on norepinephrine and serotonin transmission in the rat hippocampus. Neuropsychopharmacology. 2001;25(6):845–57.PubMedCrossRefGoogle Scholar
  72. 72.
    Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci. 2006;29:565–98.PubMedCrossRefGoogle Scholar
  73. 73.
    Preston KL, Epstein DH. Stress in the daily lives of cocaine and heroin users: relationship to mood, craving, relapse triggers, and cocaine use. Psychopharmacology (Berl). 2011;218(1):29–37.CrossRefGoogle Scholar
  74. 74.
    Graf EN, Wheeler RA, Baker DA, Ebben AL, Hill JE, McReynolds JR, et al. Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking. J Neurosci. 2013;33(29):11800–10.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Aoyama N, Takahashi N, Kitaichi K, Ishihara R, Saito S, Maeno N, et al. Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder. Alcohol Clin Exp Res. 2006;30(10):1644–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H. Drug excretion mediated by a new prototype of polyspecific transporter. Nature. 1994;372(6506):549–52.PubMedCrossRefGoogle Scholar
  77. 77.
    Haenisch B, Drescher E, Thiemer L, Xin H, Giros B, Gautron S, et al. Interaction of antidepressant and antipsychotic drugs with the human organic cation transporters hOCT1, hOCT2 and hOCT3. Naunyn Schmiedebergs Arch Pharmacol. 2012;385(10):1017–23.PubMedCrossRefGoogle Scholar
  78. 78.
    Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, et al. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000;279(3):F449–58.PubMedGoogle Scholar
  79. 79.
    Urakami Y, Akazawa M, Saito H, Okuda M, Inui K. cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002;13(7):1703–10.PubMedCrossRefGoogle Scholar
  80. 80.
    Amphoux A, Vialou V, Drescher E, Bruss M, La Cour CM, Rochat C, et al. Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006;50(8):941–52.PubMedCrossRefGoogle Scholar
  81. 81.
    Goralski KB, Lou G, Prowse MT, Gorboulev V, Volk C, Koepsell H, et al. The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. J Pharmacol Exp Ther. 2002;303(3):959–68.PubMedCrossRefGoogle Scholar
  82. 82.
    Amphoux A, Millan MJ, Cordi A, Bonisch H, Vialou V, Mannoury la Cour C, et al. Inhibitory and facilitory actions of isocyanine derivatives at human and rat organic cation transporters 1, 2 and 3: a comparison to human alpha 1- and alpha 2-adrenoceptor subtypes. Eur J Pharmacol. 2010;634(1–3):1–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Shang T, Uihlein AV, Van Asten J, Kalyanaraman B, Hillard CJ. 1-Methyl-4-phenylpyridinium accumulates in cerebellar granule neurons via organic cation transporter 3. J Neurochem. 2003;85(2):358–67.PubMedCrossRefGoogle Scholar
  84. 84.
    Rappold PM, Cui M, Chesser AS, Tibbett J, Grima JC, Duan L, et al. Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc Natl Acad Sci U S A. 2011;108(51):20766–71.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Okuda M, Saito H, Urakami Y, Takano M, Inui K. cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem Biophys Res Commun. 1996;224(2):500–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Budiman T, Bamberg E, Koepsell H, Nagel G. Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat. J Biol Chem. 2000;275(38):29413–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Minuesa G, Volk C, Molina-Arcas M, Gorboulev V, Erkizia I, Arndt P, et al. Transport of lamivudine [(-)-beta-L-2′,3′-dideoxy-3′-thiacytidine] and high-affinity interaction of nucleoside reverse transcriptase inhibitors with human organic cation transporters 1, 2, and 3. J Pharmacol Exp Ther. 2009;329(1):252–61.PubMedCrossRefGoogle Scholar
  88. 88.
    Ciarimboli G, Ludwig T, Lang D, Pavenstadt H, Koepsell H, Piechota HJ, et al. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005;167(6):1477–84.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Wenge B, Geyer J, Bonisch H. Oxybutynin and trospium are substrates of the human organic cation transporters. Naunyn Schmiedebergs Arch Pharmacol. 2011;383(2):203–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res. 2009;26(9):2039–54.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Thevenod F, Ciarimboli G, Leistner M, Wolff NA, Lee WK, Schatz I, et al. Substrate- and cell contact-dependent inhibitor affinity of human organic cation transporter 2: studies with two classical organic cation substrates and the novel substrate cd2+. Mol Pharm. 2013;10(8):3045–56.PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.French Institute of Health and Medical Research, NeuroscienceInstitute of Biology Paris-SeineParisFrance

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