Organic cation transporters: Physiology, toxicology and special focus on ethidium as a novel substrate

Current Drug Metabolism

Volumn 10, Issue 6, 2009, Pages 617-631

  Lee, Wing Kee ^a   Wolff, Natascha A ^a   Thévenod, Frank ^a  

^a UNIVERSITY OF WITTEN HERDECKE   (Germany)

Author keywords

Homidium; Phenanthridine; SLC22A; Tetraethylammonium; Toxicity

Indexed keywords

ETHIDIUM BROMIDE; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; PROPIDIUM IODIDE;

BINDING AFFINITY; BLOOD BRAIN BARRIER; BRAIN; CATION TRANSPORT; DNA BINDING; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG EXCRETION; DRUG MEGADOSE; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG TRANSPORT; DRUG UPTAKE; ENZYME SPECIFICITY; EUKARYOTE; HUMAN; HYPERTENSION; INTESTINE; KIDNEY PARENCHYMA; LIVER PARENCHYMA; NONHUMAN; PLACENTA; PROKARYOTE; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RESPIRATORY SYSTEM; REVIEW; SEX DIFFERENCE; SKIN; STRUCTURE ANALYSIS; TISSUE DISTRIBUTION; TOXICITY; TOXICOLOGY; TRANSPORT KINETICS; TRYPANOSOMIASIS;

ANIMALS; ETHIDIUM; HUMANS; ORGANIC CATION TRANSPORT PROTEINS; TRYPANOCIDAL AGENTS;

EID: 70450121903     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009789375360     Document Type: Review

References (204)

1. Ciarimboli, G. Organic cation transporters. Xenobiotica, 2008, 38(7-8), 936-971
2. Jonker, J.W.; Schinkel, A.H. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J. Pharmacol. Exp. Ther., 2004, 308(1), 2-9. (Pubitemid 38090693)
3. Koepsell, H.; Endou, H. The SLC22 drug transporter family. Pflugers. Arch., 2004, 447(5), 666-676
4. Koepsell, H.; Lips, K.; Volk, C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm. Res., 2007, 24(7), 1227-1251 (Pubitemid 46876495)
5. Devireddy, L.R.; Gazin, C.; Zhu, X.; Green, M.R. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell, 2005, 123(7), 1293-1305
6. Busch, A.E.; Quester, S.; Ulzheimer, J.C.; Waldegger, S.; Gorboulev, V.; Arndt, P.; Lang, F.; Koepsell, H. Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J. Biol. Chem., 1996, 271(51), 32599-32604 (Pubitemid 27008679)
7. Gorboulev, V.; Ulzheimer, J.C.; Akhoundova, A.; Ulzheimer-Teuber, I.; Karbach, U.; Quester, S.; Baumann, C.; Lang, F.; Busch, A.E.; Koepsell, H. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol., 1997, 16(7), 871-881 (Pubitemid 27332696)
8. Kekuda, R.; Prasad, P.D.; Wu, X.; Wang, H.; Fei, Y.J.; Leibach, F.H.; Ganapathy, V. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J. Biol. Chem., 1998, 273(26), 15971-15979
9. Urakami, Y.; Okuda, M.; Masuda, S.; Saito, H.; Inui, K.I. Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs. J. Pharmacol. Exp. Ther., 1998, 287(2), 800-805
10. Zhang, L.; Dresser, M.J.; Gray, A.T.; Yost, S.C.; Terashita, S.; Giacomini, K.M. Cloning and functional expression of a human liver organic cation transporter. Mol. Pharmacol., 1997, 51(6), 913-921
11. Wright, S.H. Role of organic cation transporters in the renal handling of therapeutic agents and xenobiotics. Toxicol. Appl. Pharmacol., 2005, 204(3), 309-319
12. Alnouti, Y.; Petrick, J.S.; Klaassen, C.D. Tissue distribution and ontogeny of organic cation transporters in mice. Drug Metab. Dispos., 2006, 34(3), 477-482 (Pubitemid 43290907)
13. Gründemann, D.; Babin-Ebell, J.; Martel, F.; Ording, N.; Schmidt, A.; Schömig, E. Primary structure and functional expression of the apical organic cation transporter from kidney epithelial LLC-PK1 cells. J. Biol. Chem., 1997, 272(16), 10408-10413 (Pubitemid 27181042)
14. Gründemann, D.; Gorboulev, V.; Gambaryan, S.; Veyhl, M.; Koepsell, H. Drug excretion mediated by a new prototype of polyspecific transporter. Nature, 1994, 372(6506), 549-552 (Pubitemid 24368536)
15. Slitt, A.L.; Cherrington, N.J.; Hartley, D.P.; Leazer, T.M.; Klaassen, C.D. Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab. Dispos., 2002, 30(2), 212-219
16. Hilgendorf, C.; Ahlin, G.; Seithel, A.; Artursson, P.; Ungell, A.L.; Karlsson, J. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab. Dispos., 2007, 35(8), 1333-1340 (Pubitemid 47121774)
17. Motohashi, H.; Sakurai, Y.; Saito, H.; Masuda, S.; Urakami, Y.; Goto, M.; Fukatsu, A.; Ogawa, O.; Inui, K. Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J. Am. Soc. Nephrol., 2002, 13(4), 866-874 (Pubitemid 34274082)
18. Meyer-Wentrup, F.; Karbach, U.; Gorboulev, V.; Arndt, P.; Koepsell, H. Membrane localization of the electrogenic cation transporter rOCT1 in rat liver. Biochem. Biophys. Res. Commun., 1998, 248(3), 673-678 (Pubitemid 28404480)
19. Karbach, U.; Kricke, J.; Meyer-Wentrup, F.; Gorboulev, V.; Volk, C.; Loffing-Cueni, D.; Kaissling, B.; Bachmann, S.; Koepsell, H. Localization of organic cation transporters OCT1 and OCT2 in rat kidney. Am. J. Physiol. Renal Physiol., 2000, 279(4), F679-87. (Pubitemid 30951502)
20. Sugawara-Yokoo, M.; Urakami, Y.; Koyama, H.; Fujikura, K.; Masuda, S.; Saito, H.; Naruse, T.; Inui, K.; Takata, K. Differential localization of organic cation transporters rOCT1 and rOCT2 in the basolateral membrane of rat kidney proximal tubules. Histochem. Cell Biol., 2000, 114(3), 175-180 (Pubitemid 30764021)
21. Chen, J.J.; Li, Z.; Pan, H.; Murphy, D.L.; Tamir, H.; Koepsell, H.; Gershon, M.D. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters. J. Neurosci., 2001, 21(16), 6348-6361
22. 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), 500-507 (Pubitemid 26268216)
23. Busch, A.E.; Karbach, U.; Miska, D.; Gorboulev, V.; Akhoundova, A.; Volk, C.; Arndt, P.; Ulzheimer, J.C.; Sonders, M.S.; Baumann, C.; Waldegger, S.; Lang, F.; Koepsell, H. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol. Pharmacol., 1998, 54(2), 342-352 (Pubitemid 28368824)
24. Amphoux, A.; Vialou, V.; Drescher, E.; Bruss, M.; Mannoury La Cour, C.; Rochat, C.; Millan, M.J.; Giros, B.; Bonisch, H.; Gautron, S. Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology, 2006, 50(8), 941-952 (Pubitemid 43810126)
25. Sweet, D.H.; Miller, D.S.; Pritchard, J.B. Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J. Biol. Chem., 2001, 276(45), 41611-41619 (Pubitemid 37371052)
26. Leazer, T.M.; Klaassen, C.D. The presence of xenobiotic transporters in rat placenta. Drug Metab. Dispos., 2003, 31(2), 153-167
27. Sata, R.; Ohtani, H.; Tsujimoto, M.; Murakami, H.; Koyabu, N.; Nakamura, T.; Uchiumi, T.; Kuwano, M.; Nagata, H.; Tsukimori, K.; Nakano, H.; Sawada, Y. Functional analysis of organic cation transporter 3 expressed in human placenta. J. Pharmacol. Exp. Ther., 2005, 315(2), 888-895 (Pubitemid 41500755)
28. Verhaagh, S.; Schweifer, N.; Barlow, D.P.; Zwart, R. Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27. Genomics, 1999, 55(2), 209-218 (Pubitemid 29093516)
29. Wu, X.; Huang, W.; Ganapathy, M.E.; Wang, H.; Kekuda, R.; Conway, S.J.; Leibach, F.H.; Ganapathy, V. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am. J. Physiol. Renal Physiol., 2000, 279(3), F449-58.
30. 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), 291-297 (Pubitemid 38084545)
31. 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), 2846-2851 (Pubitemid 38380963)
32. Groves, C.E.; Suhre, W.B.; Cherrington, N.J.; Wright, S.H. Sex differences in the mRNA, protein, and functional expression of organic anion transporter (Oat) 1, Oat3, and organic cation transporter (Oct) 2 in rabbit renal proximal tubules. J. Pharmacol. Exp. Ther., 2006, 316(2), 743-752
33. Urakami, Y.; Nakamura, N.; Takahashi, K.; Okuda, M.; Saito, H.; Hashimoto, Y.; Inui, K. Gender differences in expression of organic cation transporter OCT2 in rat kidney. FEBS. Lett., 1999, 461(3), 339-342 (Pubitemid 29533359)
34. Bowman, H.M.; Hook, J.B. Sex differences in organic ion transport by rat kidney. Proc. Soc. Exp. Biol. Med., 1972, 141(1), 258-262
35. Yonezawa, A.; Masuda, S.; Nishihara, K.; Yano, I.; Katsura, T.; Inui, K. Association between tubular toxicity of cisplatin and expression of organic cation transporter rOCT2 (Slc22a2) in the rat. Biochem. Pharmacol., 2005, 70(12), 1823-1831 (Pubitemid 41612013)
36. Wright, S.H.; Evans, K.K.; Zhang, X.; Cherrington, N.J.; Sitar, D.S.; Dantzler, W.H. Functional map of TEA transport activity in isolated rabbit renal proximal tubules. Am. J. Physiol. Renal Physiol., 2004, 287(3), F442-51.
37. Goralski, K.B.; Lou, G.; Prowse, M.T.; Gorboulev, V.; Volk, C.; Koepsell, H.; Sitar, D.S. 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), 959-968
38. Wong, L.T.; Sitar, D.S.; Aoki, F.Y. Chronic tobacco smoking and gender as variables affecting amantadine disposition in healthy subjects. Br. J. Clin. Pharmacol., 1995, 39(1), 81-84
39. Meijer, D.K.; Mol, W.E.; Muller, M.; Kurz, G. Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations. J. Pharmacokinet. Biopharm., 1990, 18(1), 35-70. (Pubitemid 20227241)
40. Chen, Y.; Zhang, S.; Sorani, M.; Giacomini, K.M. Transport of paraquat by human organic cation transporters and multidrug and toxic compound extrusion family. J. Pharmacol. Exp. Ther., 2007, 322(2), 695-700.
41. Harlfinger, S.; Fork, C.; Lazar, A.; Schomig, E.; Grundemann, D. Are organic cation transporters capable of transporting prostaglandins? Naunyn. Schmiedebergs. Arch. Pharmacol., 2005, 372(2), 125-130 (Pubitemid 41504159)
42. Kimura, H.; Takeda, M.; Narikawa, S.; Enomoto, A.; Ichida, K.; Endou, H. Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J. Pharmacol. Exp. Ther., 2002, 301(1), 293-298 (Pubitemid 34250307)
43. Zhang, L.; Gorset, W.; Dresser, M.J.; Giacomini, K.M. The interaction of n-tetraalkylammonium compounds with a human organic cation transporter, hOCT1. J. Pharmacol. Exp. Ther., 1999, 288(3), 1192-1198
44. Lee, W.K.; Reichold, M.; Edemir, B.; Ciarimboli, G.; Warth, R.; Koepsell, H.; Thevenod, F. The organic cation transporters OCT1, 2, and 3 mediate high affinity transport of the mutagenic vital dye ethidium in the kidney proximal tubule. Am. J. Physiol. Renal Physiol., 2009, 296(6), F1504-13.
45. Seithel, A.; Karlsson, J.; Hilgendorf, C.; Bjorquist, A.; Ungell, A.L. Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells. Eur. J. Pharm. Sci., 2006, 28(4), 291-299 (Pubitemid 44218740)
46. Gründemann, D.; Liebich, G.; Kiefer, N.; Koster, S.; Schömig, E. Selective substrates for non-neuronal monoamine transporters. Mol. Pharmacol., 1999, 56(1), 1-10. (Pubitemid 29309806)
47. Zhang, X.; Groves, C.E.; Bahn, A.; Barendt, W.M.; Prado, M.D.; Rodiger, M.; Chatsudthipong, V.; Burckhardt, G.; Wright, S.H. Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule. Am. J. Physiol. Renal Physiol., 2004, 287(5), F999-1010.
48. Arndt, P.; Volk, C.; Gorboulev, V.; Budiman, T.; Popp, C.; Ulzheimer-Teuber, I.; Akhoundova, A.; Koppatz, S.; Bamberg, E.; Nagel, G.; Koepsell, H. Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am. J. Physiol. Renal Physiol., 2001, 281(3), F454-68. (Pubitemid 32885130)
49. Gründemann, D.; Schechinger, B.; Rappold, G.A.; Schömig, E. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat. Neurosci., 1998, 1(5), 349-351
50. Wu, X.; Kekuda, R.; Huang, W.; Fei, Y.J.; Leibach, F.H.; Chen, J.; Conway, S.J.; Ganapathy, V. 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), 32776-32786 (Pubitemid 28557664)
51. Schömig, E.; Lazar, A.; Gründemann, D. Extraneuronal monoamine transporter and organic cation transporters 1 and 2: a review of transport efficiency. Handb. Exp. Pharmacol., 2006, 175, 151-80.anachem.
52. Umehara, K.I.; Iwatsubo, T.; Noguchi, K.; Kamimura, H. Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates. Xenobiotica., 2007, 37(6), 618-634 (Pubitemid 47037155)
53. Masuda, S.; Terada, T.; Yonezawa, A.; Tanihara, Y.; Kishimoto, K.; Katsura, T.; Ogawa, O.; Inui, K. Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J. Am. Soc. Nephrol., 2006, 17(8), 2127-2135 (Pubitemid 44141902)
54. Ohta, K.Y.; Inoue, K.; Hayashi, Y.; Yuasa, H. Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab. Dispos., 2006, 34(11), 1868-1874 (Pubitemid 44771715)
55. Pietig, G.; Mehrens, T.; Hirsch, J.R.; Cetinkaya, I.; Piechota, H.; Schlatter, E. Properties and regulation of organic cation transport in freshly isolated human proximal tubules. J. Biol. Chem., 2001, 276(36), 33741-33746 (Pubitemid 37384593)
56. Takeda, M.; Khamdang, S.; Narikawa, S.; Kimura, H.; Kobayashi, Y.; Yamamoto, T.; Cha, S.H.; Sekine, T.; Endou, H. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J. Pharmacol. Exp. Ther., 2002, 300(3), 918-924 (Pubitemid 34164996)
57. Gründemann, D.; Koster, S.; Kiefer, N.; Breidert, T.; Engelhardt, M.; Spitzenberger, F.; Obermüller, N.; Schömig, E. Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J. Biol. Chem., 1998, 273(47), 30915-30920 (Pubitemid 28533093)
58. Yu, P.; Asico, L.D.; Luo, Y.; Andrews, P.; Eisner, G.M.; Hopfer, U.; Felder, R.A.; Jose, P.A. D1 dopamine receptor hyperphosphorylation in renal proximal tubules in hypertension. Kidney Int., 2006b, 70(6), 1072-1079 (Pubitemid 44344077)
59. Zeng, C.; Yang, Z.; Wang, Z.; Jones, J.; Wang, X.; Altea, J.; Mangrum, A.J.; Hopfer, U.; Sibley, D.R.; Eisner, G.M.; Felder, R.A.; Jose, P.A. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension, 2005, 45(4), 804-810
60. O'Connell, D.P.; Botkin, S.J.; Ramos, S.I.; Sibley, D.R.; Ariano, M.A.; Felder, R.A.; Carey, R.M. Localization of dopamine D1A receptor protein in rat kidneys. Am. J. Physiol., 1995, 268(6 Pt 2), F1185-97.
61. O'Connell, D.P.; Vaughan, C.J.; Aherne, A.M.; Botkin, S.J.; Wang, Z.Q.; Felder, R.A.; Carey, R.M. Expression of the dopamine D3 receptor protein in the rat kidney. Hypertension, 1998, 32(5), 886-895 (Pubitemid 28530224)
62. Cinelli, A.R.; Efendiev, R.; Pedemonte, C.H. Trafficking of Na-K-ATPase and dopamine receptor molecules induced by changes in intracellular sodium concentration of renal epithelial cells. Am. J. Physiol. Renal Physiol., 2008, 295(4), F1117-25.
63. Trivedi, M.; Narkar, V.A.; Hussain, T.; Lokhandwala, M.F. Dopamine recruits D1A receptors to Na-K-ATPase-rich caveolar plasma membranes in rat renal proximal tubules. Am. J. Physiol. Renal Physiol., 2004, 287(5), F921-31.
64. Nürnberger, A.; Rabiger, M.; Mack, A.; Diaz, J.; Sokoloff, P.; Muhlbauer, B.; Luippold, G. Subapical localization of the dopamine D3 receptor in proximal tubules of the rat kidney. J. Histochem. Cytochem., 2004, 52(12), 1647-1655 (Pubitemid 39603263)
65. Hagege, J.; Richet, G. Proximal tubule dopamine histofluorescence in renal slices incubated with L-dopa. Kidney Int., 1985, 27(1), 3-8. (Pubitemid 15130678)
66. Jonker, J.W.; Wagenaar, E.; Van Eijl, S.; Schinkel, A.H. 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), 7902-7908
67. Eisenhofer, G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol. Ther., 2001, 91(1), 35-62. (Pubitemid 33055773)
68. Inazu, M.; Takeda, H.; Matsumiya, T. Expression and functional characterization of the extraneuronal monoamine transporter in normal human astrocytes. J. Neurochem., 2003, 84(1), 43-52. (Pubitemid 36182064)
69. Baganz, N.L.; Horton, R.E.; Calderon, A.S.; Owens, W.A.; Munn, J.L.; Watts, L.T.; Koldzic-Zivanovic, N.; Jeske, N.A.; Koek, W.; Toney, G.M.; Daws, L.C. Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc. Natl. Acad. Sci. USA, 2008, 105(48), 18976-18981
70. Rajan, P.D.; Kekuda, R.; Chancy, C.D.; Huang, W.; Ganapathy, V.; Smith, S.B. Expression of the extraneuronal monoamine transporter in RPE and neural retina. Curr. Eye Res., 2000, 20(3), 195-204.
71. Vialou, V.; Balasse, L.; Callebert, J.; Launay, J.M.; Giros, B.; Gautron, S. Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice. J. Neurochem., 2008, 106(3), 1471-1482
72. Lips, K.S.; Volk, C.; Schmitt, B.M.; Pfeil, U.; Arndt, P.; Miska, D.; Ermert, L.; Kummer, W.; Koepsell, H. Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Am. J. Respir. Cell Mol. Biol., 2005, 33(1), 79-88. (Pubitemid 40961017)
73. Reinheimer, T.; Bernedo, P.; Klapproth, H.; Oelert, H.; Zeiske, B.; Racke, K.; Wessler, I. Acetylcholine in isolated airways of rat, guinea pig, and human: species differences in role of airway mucosa. Am. J. Physiol., 1996, 270(5 Pt 1), L722-8. (Pubitemid 126756762)
74. Reinheimer, T.; Munch, M.; Bittinger, F.; Racke, K.; Kirkpatrick, C.J.; Wessler, I. Glucocorticoids mediate reduction of epithelial acetylcholine content in the airways of rats and humans. Eur. J. Pharmacol., 1998, 349(2-3), 277-284 (Pubitemid 28277098)
75. Proskocil, B.J.; Sekhon, H.S.; Jia, Y.; Savchenko, V.; Blakely, R.D.; Lindstrom, J.; Spindel, E.R. Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells. Endocrinology, 2004, 145(5), 2498-2506
76. Kummer, W.; Lips, K.S.; Pfeil, U. The epithelial cholinergic system of the airways. Histochem. Cell Biol., 2008, 130(2), 219-234
77. Ehrhardt, C.; Kneuer, C.; Laue, M.; Schaefer, U.F.; Kim, K.J.; Lehr, C.M. 16HBE14o- human bronchial epithelial cell layers express P-glycoprotein, lung resistance-related protein, and caveolin-1. Pharm. Res., 2003, 20(4), 545-551
78. Lechapt-Zalcman, E.; Hurbain, I.; Lacave, R.; Commo, F.; Urban, T.; Antoine, M.; Milleron, B.; Bernaudin, J.F. MDR1-Pgp 170 expression in human bronchus. Eur. Respir. J., 1997, 10(8), 1837-1843
79. Ehrhardt, C.; Collnot, E.M.; Baldes, C.; Becker, U.; Laue, M.; Kim, K.J.; Lehr, C.M. Towards an in vitro model of cystic fibrosis small airway epithelium: characterisation of the human bronchial epithelial cell line CFBE41o. Cell Tissue Res., 2006, 323(3), 405-415
80. Lin, Y.; Shen, Q.; Katsumi, H.; Okada, N.; Fujita, T.; Jiang, X.; Yamamoto, A. Effects of Labrasol and other pharmaceutical excipients on the intestinal transport and absorption of rhodamine123, a P-glycoprotein substrate, in rats. Biol. Pharm. Bull., 2007, 30(7), 1301-1307 (Pubitemid 47037658)
81. Ehrhardt, C.; Kneuer, C.; Bies, C.; Lehr, C.M.; Kim, K.J.; Bakowsky, U. Salbutamol is actively absorbed across human bronchial epithelial cell layers. Pulm. Pharmacol. Ther., 2005, 18(3), 165-170 (Pubitemid 40222110)
82. Duffy, K.A.; Attkins, N.; Gardiner, I.; Smith, D.A.; Hawksworth, G.M. Can transfected cell lines predict renal clearance in man? Toxicology, 2006, 226(1), 67-68.
83. Ganapathy, V.; Prasad, P.D. Role of transporters in placental transfer of drugs. Toxicol. Appl. Pharmacol., 2005, 207(2 Suppl), 381-387
84. Ganapathy, V.; Prasad, P.D.; Ganapathy, M.E.; Leibach, F.H. Placental transporters relevant to drug distribution across the maternalfetal interface. J. Pharmacol. Exp. Ther., 2000, 294(2), 413-420
85. Bzoskie, L.; Blount, L.; Kashiwai, K.; Humme, J.; Padbury, J.F. The contribution of transporter-dependent uptake to fetal catecholamine clearance. Biol. Neonate., 1997, 71(2), 102-110 (Pubitemid 27086940)
86. Bzoskie, L.; Blount, L.; Kashiwai, K.; Tseng, Y.T.; Hay, W.W., Jr.; Padbury, J.F. Placental norepinephrine clearance: in vivo measurement and physiological role. Am. J. Physiol., 1995, 269(1 Pt 1), E145-9.
87. Zwart, R.; Verhaagh, S.; Buitelaar, M.; Popp-Snijders, C.; Barlow, D.P. Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice. Mol. Cell Biol., 2001, 21(13), 4188-4196
88. Müller, J.; Lips, K.S.; Metzner, L.; Neubert, R.H.; Koepsell, H.; Brandsch, M. Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem. Pharmacol., 2005, 70(12), 1851-1860 (Pubitemid 41612016)
89. Waring, M.J. Complex formation between ethidium bromide and nucleic acids. J. Mol. Biol., 1965, 13(1), 269-282
90. LePecq, J.B.; Paoletti, C. A new fluorometric method for RNA and DNA determination. Anal. Biochem., 1966, 17(1), 100-107
91. LePecq, J.B.; Paoletti, C. A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization. J. Mol. Biol., 1967, 27(1), 87-106.
92. Lakowicz, J.R. Principles of Fluorescence Spectroscopy. 3rd ed.; Springer: New York, 2006.
93. Borst, P. Ethidium DNA agarose gel electrophoresis: how it started. IUBMB Life, 2005, 57(11), 745-747 (Pubitemid 41770190)
94. Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res., 1988, 175(1), 184-191
95. Ormerod, M.G.; Kubbies, M. Cell cycle analysis of asynchronous cell populations by flow cytometry using bromodeoxyuridine label and Hoechst-propidium iodide stain. Cytometry, 1992, 13(7), 678-685
96. Liegler, T.J.; Hyun, W.; Yen, T.S.; Stites, D.P. Detection and quantification of live, apoptotic, and necrotic human peripheral lymphocytes by single-laser flow cytometry. Clin. Diagn. Lab. Immunol., 1995, 2(3), 369-376
97. Darzynkiewicz, Z. Differential staining of DNA and RNA in intact cells and isolated cell nuclei with acridine orange. Methods Cell Biol., 1990, 33, 285-298
98. Goebel, D.J.; Winkler, B.S. Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only partial neuroprotection against NMDA-induced cell death in the rat retina. J. Neurochem., 2006, 98(6), 1732-1745
99. Lee, W.K.; Abouhamed, M.; Thevenod, F. Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells. Am. J. Physiol. Renal. Physiol., 2006, 291(4), F823-32.
100. Schilling, W.P.; Snyder, D.; Sinkins, W.G.; Estacion, M. Palytoxin-induced cell death cascade in bovine aortic endothelial cells. Am. J. Physiol. Cell Physiol., 2006, 291(4), C657-67. (Pubitemid 44497592)
101. Baskic, D.; Popovic, S.; Ristic, P.; Arsenijevic, N.N. Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol. Int., 2006, 30(11), 924-932
102. Hastings, R.H.; Quintana, R.A.; Sandoval, R.; Duey, D.; Rascon, Y.; Burton, D.W.; Deftos, L.J. Proapoptotic effects of parathyroid hormone-related protein in type II pneumocytes. Am. J. Respir. Cell Mol. Biol., 2003, 29(6), 733-742
103. Darzynkiewicz, Z.; Bruno, S.; Del Bino, G.; Gorczyca, W.; Hotz, M.A.; Lassota, P.; Traganos, F. Features of apoptotic cells measured by flow cytometry. Cytometry, 1992, 13(8), 795-808.
104. Krishan, A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J. Cell Biol., 1975, 66(1), 188-193
105. Moore, A.; Donahue, C.J.; Bauer, K.D.; Mather, J.P. Simultaneous measurement of cell cycle and apoptotic cell death. Methods Cell Biol., 1998, 57, 265-278 (Pubitemid 128787445)
106. Taylor, P.; Lappi, S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry, 1975, 14(9), 1989-1997
107. Fukunaga, M.; Yielding, K.L. Antagonism by propidium of petite induction by ethidium and ethidium azide in Saccharomyces cerevisiae. Mutat. Res., 1979, 62 (1), 35-42.
108. Mazurkiewicz, P.; Poelarends, G.J.; Driessen, A.J.; Konings, W.N. Facilitated drug influx by an energy-uncoupled secondary multidrug transporter. J. Biol. Chem., 2004, 279(1), 103-108
109. Balakrishnan, L.; Venter, H.; Shilling, R.A.; van Veen, H.W. Reversible transport by the ATP-binding cassette multidrug export pump LmrA: ATP synthesis at the expense of downhill ethidium uptake. J. Biol. Chem., 2004, 279(12), 11273-11280
110. Jernaes, M.W.; Steen, H.B. Staining of Escherichia coli for flow cytometry: influx and efflux of ethidium bromide. Cytometry, 1994, 17(4), 302-309 (Pubitemid 24372413)
111. Lambert, B.; Le Pecq, J.B. Effect of mutation, electric membrane potential, and metabolic inhibitors on the accessibility of nucleic acids to ethidium bromide in Escherichia coli cells. Biochemistry, 1984, 23(1), 166-176
112. Purewal, A.S.; Jones, I.G.; Midgley, M. Cloning of the ethidium efflux gene from Escherichia coli. FEMS. Microbiol. Lett., 1990, 56(1-2), 73-76 (Pubitemid 20079605)
113. Neyfakh, A.A.; Bidnenko, V.E.; Chen, L.B. Efflux-mediated multidrug resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system. Proc. Natl. Acad. Sci. USA, 1991, 88(11), 4781-4785
114. Sasatsu, M.; Shibata, Y.; Noguchi, N.; Kono, M. High-level resistance to ethidium bromide and antiseptics in Staphylococcus aureus. FEMS. Microbiol. Lett., 1992, 72(2), 109-113
115. Lewis, K. Multidrug resistance pumps in bacteria: variations on a theme. Trends Biochem. Sci., 1994, 19(3), 119-123 (Pubitemid 24082789)
116. Pena, A.; Ramirez, G. Interaction of ethidium bromide with the transport system for monovalent cations in yeast. J. Membr. Biol., 1975, 22(3-4), 369-384
117. Coolbear, K.P.; Midgley, M. Characteristics of ethidium uptake by the trypanosomatid flagellates Crithidia fasciculata and Leptomonas seymouri. Antimicrob. Agents Chemother., 1986, 29(2), 258-262 (Pubitemid 16162935)
118. Hawking, F.; Sen, A.B. The trypanocidal action of homidium, quinapyramine and suramin. Br. J. Pharmacol. Chemother., 1960, 15, 567-570
119. Wiley, J.S.; Chen, R.; Jamieson, G.P. The ATP4- receptor-operated channel (P2Z class) of human lymphocytes allows Ba2+ and ethidium + uptake: inhibition of fluxes by suramin. Arch. Biochem. Biophys., 1993, 305(1), 54-60.
120. Surprenant, A.; Rassendren, F.; Kawashima, E.; North, R.A.; Buell, G. The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science, 1996, 272(5262), 735-738 (Pubitemid 26152784)
121. Fernando, K.C.; Gargett, C.E.; Wiley, J.S. Activation of the P2Z/P2X7 receptor in human lymphocytes produces a delayed permeability lesion: involvement of phospholipase D. Arch. Biochem. Biophys., 1999, 362(2), 197-202.
122. Lajdova, I.; Chorvat, D., Jr.; Spustova, V.; Chorvatova, A. 4-Aminopyridine activates calcium influx through modulation of the pore-forming purinergic receptor in human peripheral blood mononuclear cells. Can. J. Physiol. Pharmacol., 2004, 82(1), 50-56 (Pubitemid 38420837)
123. Virginio, C.; Church, D.; North, R.A.; Surprenant, A. Effects of divalent cations, protons and calmidazolium at the rat P2X7 receptor. Neuropharmacology, 1997, 36(9), 1285-1294 (Pubitemid 27465616)
124. Spengler, G.; Viveiros, M.; Martins, M.; Rodrigues, L.; Martins, A.; Molnar, J.; Couto, I.; Amaral, L. Demonstration of the activity of P-glycoprotein by a semi-automated fluorometric method. Anticancer Res., 2009, 29(6), 2173-2177
125. Bosmann, H.B.; MacGregor, J.T. Inhibition of macromolecular synthesis in Escherichia coli, L5178Y cells, and mitochondria by ethidium bromide, related compounds, and metabolites. Biochem. Pharmacol., 1971, 20(10), 2921-2926
126. Tomchick, R.; Mandel, H.G. Biochemical effects of ethidium bromide in micro-organisms. J. Gen. Microbiol., 1964, 36, 225-236
127. Waring, M.J. Complex formation with DNA and inhibition of Escherichia coli RNA polymerase by ethidium bromide. Biochim. Biophys. Acta., 1964, 87, 358-361
128. Burns, V.W. Location and molecular characteristics of fluorescent complexes of ethidium bromide in the cell. Exp. Cell Res., 1972, 75(1), 200-206
129. Boibessot, I.; Turner, C.M.; Watson, D.G.; Goldie, E.; Connel, G.; McIntosh, A.; Grant, M.H.; Skellern, G.G. Metabolism and distribution of phenanthridine trypanocides in Trypanosoma brucei. Acta. Trop., 2002, 84(3), 219-228
130. Fukuhara, H.; Kujawa, C. Selective inhibition of the in vivo transcription of mitochondrial DNA by ethidium bromide and by acriflavin. Biochem. Biophys. Res. Commun., 1970, 41(4), 1002-1008
131. Goldring, E.S.; Grossman, L.I.; Krupnick, D.; Cryer, D.R.; Marmur, J. The petite mutation in yeast. Loss of mitochondrial deoxyribonucleic acid during induction of petites with ethidium bromide. J. Mol. Biol., 1970, 52(2), 323-335
132. Pena, A.; Chavez, E.; Carabez, A.; De Gomez-Puyou, M.T. The metabolic effects and uptake of ethidium bromide by rat liver mitochondria. Arch. Biochem. Biophys., 1977, 180(2), 522-529 (Pubitemid 8115523)
133. Berman, J.J. Ethidium bromide resistance in a rat liver epithelial cell line: association with enhanced drug efflux. Cell Biol. Toxicol., 1988, 4(3), 325-332
134. Armand, R.; Channon, J.Y.; Kintner, J.; White, K.A.; Miselis, K.A.; Perez, R.P.; Lewis, L.D. The effects of ethidium bromide induced loss of mitochondrial DNA on mitochondrial phenotype and ultrastructure in a human leukemia T-cell line (MOLT-4 cells). Toxicol. Appl. Pharmacol., 2004, 196(1), 68-79.
135. Leibowitz, R.D. The effect of ethidium bromide on mitochondrial DNA synthesis and mitochondrial DNA structure in HeLa cells. J. Cell Biol., 1971, 51(1), 116-122
136. Nass, M.M. Differential effects of ethidium bromide on mitochondrial and nuclear DNA synthesis in vivo in cultured mammalian cells. Exp. Cell Res., 1972, 72(1), 211-222
137. Radsak, K.; Kato, K.; Sato, N.; Koprowski, H. Effect of ethidium bromide on mitochondrial DNA and cytochrome synthesis in HeLa cells. Exp. Cell Res., 1971, 66(2), 410-416
138. Yu, M.; Shi, Y.; Wei, X.; Yang, Y.; Zhou, Y.; Hao, X.; Zhang, N.; Niu, R. Depletion of mitochondrial DNA by ethidium bromide treatment inhibits the proliferation and tumorigenesis of T47D human breast cancer cells. Toxicol. Lett., 2007, 170(1), 83-93. (Pubitemid 46498907)
139. Meyer, R.R.; Simpson, M.V. DNA biosynthesis in mitochondria. Differential inhibition of mitochondrial and nuclear DNA polymerases by the mutagenic dyes ethidium bromide and acriflavin. Biochem. Biophys. Res. Commun., 1969, 34(2), 238-244
140. Hayakawa, T.; Noda, M.; Yasuda, K.; Yorifuji, H.; Taniguchi, S.; Miwa, I.; Sakura, H.; Terauchi, Y.; Hayashi, J.; Sharp, G.W.; Kanazawa, Y.; Akanuma, Y.; Yazaki, Y.; Kadowaki, T. Ethidium bromide-induced inhibition of mitochondrial gene transcription suppresses glucose-stimulated insulin release in the mouse pancreatic beta-cell line betaHC9. J. Biol. Chem., 1998, 273(32), 20300-20307 (Pubitemid 28377593)
141. Blakemore, W.F. The response of oligodendrocytes to chemical injury. Acta. Neurol. Scand. Suppl., 1984, 100, 33-38
142. Carelli, V.; Bellan, M. Myelin, mitochondria, and autoimmunity: what's the connection? Neurology, 2008, 70(13 Pt 2), 1075-1076
143. Yajima, K.; Suzuki, K. Ultrastructural changes of oligodendroglia and myelin sheaths induced by ethidium bromide. Neuropathol. Appl. Neurobiol., 1979, 5(1), 49-62. (Pubitemid 10000287)
144. Higgins, E.S.; Dunlavey, B.L.; Friend, W.H.; Rogers, K.S. Ethidium bromide inhibits mitochondrial phosphorylating oxidation. Proc. Soc. Exp. Biol. Med., 1975, 149(4), 1055-1058
145. Stuchell, R.N.; Weinstein, B.I.; Beattie, D.S. Effects of ethidium bromide on the respiratory chain and oligomycin-sensitive adenosine triphosphatase in purified mitochondria from the cellular slime mold Dicyostelium discoideum. J. Biol. Chem., 1975, 250(2), 570-576
146. Klietmann, W.; Kato, K.; Gabara, B.; Koprowski, H.; Sato, N. Stable alterations in HeLa cell mitochondria following ethidium bromide treatment. Exp. Cell Res., 1973, 78(1), 47-58.
147. Roding, J.; Naujok, A.; Zimmermann, H.W. Effects of ethidium bromide, tetramethylethidium bromide and betaine B on the ultrastructure of HeLa cell mitochondria in situ. A comparative binding study. Histochemistry, 1986, 85(3), 215-222
148. Soslau, G.; Nass, M.M. Effects of ethidium bromide on the cytochrome content and ultrastructure of L cell mitochondria. J. Cell Biol., 1971, 51(21), 514-524
149. Turner, P.R.; Denny, W.A. The mutagenic properties of DNA minor-groove binding ligands. Mutat. Res., 1996, 355(1-2), 141-169
150. Courchesne, C.L.; Bantle, J.A. Analysis of the activity of DNA, RNA, and protein synthesis inhibitors on Xenopus embryo development. Teratog. Carcinog. Mutagen., 1985, 5(3), 177-193
151. Nishiwaki, H.; Miura, M.; Imai, K.; Ono, R.; Kawashima, K. Experimental studies on the antitumor effect of ethidium bromide and related substances. Cancer Res., 1974, 34(10), 2699-2703
152. Shubber, E.K.; Kram, D.; Williams, J. In vitro assay of cytogenetic damage induced in bone marrow cells in vivo by chemical carcinogens. Jpn. J. Med. Sci. Biol., 1985, 38(5-6), 207-216 (Pubitemid 16132097)
153. Vacquier, V.D.; Brachet, J. Chromosomal abnormalities resulting from ethidium bromide treatment. Nature, 1969, 222(5189), 193-195
154. Heinen, E.; Bassleer, R.; Calberg, C.M. Comparison of the effects of ethidium bromide and of ethidium bromide-deoxyribonucleic acid complex in fibroblasts cultivated in vitro. Beitr. Pathol., 1976, 159(2), 207-218
155. Meyer, R.R.; Boyd, C.R.; Rein, D.C.; Keller, S.J. Effects of ethidium bromide on growth and morphology of Tetrahymena pyriformis. Exp. Cell Res., 1972, 70(1), 233-237
156. Yajima, K.; Suzuki, K. Demyelination and remyelination in the rat central nervous system following ethidium bromide injection. Lab Invest., 1979, 41(5), 385-392 (Pubitemid 10194642)
157. Watkins, T.I.; Woolfe, G. Effect of changing the quaternizing group on the trypanocidal activity of dimidium bromide. Nature, 1952, 169(4299), 506-507
158. Dolan, R.B.; Okech, G.; Alushula, H.; Mutugi, M.; Stevenson, P.; Sayer, P.D.; Njogu, A.R. Homidium bromide as a chemoprophylactic for cattle trypanosomiasis in Kenya. Acta. Trop., 1990, 47(3), 137-144
159. Finelle, P. African animal trypanosomiasis. World Anim. Rev., 1973, 7, 1-6.
160. Melhorn, H. Encyclopedia of Parasitology: N-Z. 3rd ed.; Springer: Berlin, 2008; Vol.2.
161. Whittico, M.T.; Gang, Y.A.; Giacomini, K.M. Cimetidine transport in isolated brush border membrane vesicles from bovine choroid plexus. J. Pharmacol. Exp. Ther., 1990, 255(2), 615-623
162. Chemuturi, N.V.; Donovan, M.D. Role of organic cation transporters in dopamine uptake across olfactory and nasal respiratory tissues. Mol. Pharm., 2007, 4(6), 936-942
163. Murilla, G.A.; Mdachi, R.E.; Ismail, A.A.; Karanja, W.M. Bioavailability, pharmacokinetics, and tissue distribution of 14C homidium after parenteral administration to Boran cattle. J. Vet. Pharmacol. Ther., 1996, 19(2), 142-148
164. Fujita, T.; Urban, T.J.; Leabman, M.K.; Fujita, K.; Giacomini, K.M. Transport of drugs in the kidney by the human organic cation transporter, OCT2 and its genetic variants. J. Pharm. Sci., 2006, 95(1), 25-36.
165. Koepsell, H.; Schmitt, B.M.; Gorboulev, V. Organic cation transporters. Rev. Physiol. Biochem. Pharmacol., 2003, 150, 36-90.
166. Suhre, W.M.; Ekins, S.; Chang, C.; Swaan, P.W.; Wright, S.H. Molecular determinants of substrate/inhibitor binding to the human and rabbit renal organic cation transporters hOCT2 and rbOCT2. Mol. Pharmacol., 2005, 67(4), 1067-1077
167. Tahara, H.; Kusuhara, H.; Endou, H.; Koepsell, H.; Imaoka, T.; Fuse, E.; Sugiyama, Y. A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J. Pharmacol. Exp. Ther., 2005, 315(1), 337-345 (Pubitemid 41380529)
168. Bednarczyk, D.; Ekins, S.; Wikel, J.H.; Wright, S.H. Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol., 2003, 63(3), 489-498
169. Popp, C.; Gorboulev, V.; Muller, T.D.; Gorbunov, D.; Shatskaya, N.; Koepsell, H. Amino acids critical for substrate affinity of rat organic cation transporter 1 line the substrate binding region in a model derived from the tertiary structure of lactose permease. Mol. Pharmacol., 2005, 67(5), 1600-1611 (Pubitemid 40594159)
170. Minuesa, G.; Volk, C.; Molina-Arcas, M.; Gorboulev, V.; Erkizia, I.; Arndt, P.; Clotet, B.; Pastor-Anglada, M.; Koepsell, H.; Martinez-Picado, J. 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), 252-261
171. Stachon, A.; Hohage, H.; Feidt, C.; Schlatter, E. Characterisation of organic cation transport across the apical membrane of proximal tubular cells with the fluorescent dye 4-Di-1-ASP. Cell Physiol. Biochem., 1997, 7(5), 265-274. (Pubitemid 27430017)
172. Dohgu, S.; Yamauchi, A.; Takata, F.; Sawada, Y.; Higuchi, S.; Naito, M.; Tsuruo, T.; Shirabe, S.; Niwa, M.; Katamine, S.; Kataoka, Y. Uptake and efflux of quinacrine, a candidate for the treatment of prion diseases, at the blood-brain barrier. Cell Mol. Neurobiol., 2004, 24(2), 205-217
173. Sweet, D.H.; Pritchard, J.B. rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger. Am. J. Physiol., 1999, 277(6 Pt 2), F890-8.
174. Ciarimboli, G.; Koepsell, H.; Iordanova, M.; Gorboulev, V.; Durner, B.; Lang, D.; Edemir, B.; Schroter, R.; Van Le, T.; Schlatter, E. Individual PKC-phosphorylation sites in organic cation transporter 1 determine substrate selectivity and transport regulation. J. Am. Soc. Nephrol., 2005, 16(6), 1562-1570 (Pubitemid 41716463)
175. Gorbunov, D.; Gorboulev, V.; Shatskaya, N.; Mueller, T.; Bamberg, E.; Friedrich, T.; Koepsell, H. High-affinity cation binding to organic cation transporter 1 induces movement of helix 11 and blocks transport after mutations in a modeled interaction domain between two helices. Mol. Pharmacol., 2008, 73.(1), 50-61. (Pubitemid 350294196)
176. Schmitt, B.M.; Gorbunov, D.; Schlachtbauer, P.; Egenberger, B.; Gorboulev, V.; Wischmeyer, E.; Muller, T.; Koepsell, H. Charge-to-substrate ratio during organic cation uptake by rat OCT2 is voltage dependent and altered by exchange of glutamate 448 with glutamine. Am. J. Physiol. Renal. Physiol., 2009, 296(4), F709-22.
177. Palissot, V.; Liautaud-Roger, F.; Carpentier, Y.; Dufer, J. Analysis of DNA content in multidrug-resistant cells by image and flow cytometry. Cell Prolif., 1996, 29(10), 549-559 (Pubitemid 27101582)
178. Moe, O.W.; Wright, S.H.; Palacin, M. In Brenner & Rector's The Kidney 8th ed.; Brenner, B.M., Ed. Saunders Elsevier: Philadelphia, 2008; Vol.1, pp. 214-247.
179. Baum, M. The cellular basis of Fanconi syndrome. Hosp. Pract. (Off Ed)., 1993, 28(11), 137-42, 147-148
180. Hillman, K.A.; Burnstock, G.; Unwin, R.J. The P2X7 ATP receptor in the kidney: a matter of life or death? Nephron Exp. Nephrol., 2005, 101(1), e24-30.
181. Emmett, D.S.; Feranchak, A.; Kilic, G.; Puljak, L.; Miller, B.; Dolovcak, S.; McWilliams, R.; Doctor, R.B.; Fitz, J.G. Characterization of ionotrophic purinergic receptors in hepatocytes. Hepatology, 2008, 47(2), 698-705.
182. Cesarini, K.; Bigotte, L.; Olsson, Y. Fluorescence-microscopic localization of in vivo injected ethidium bromide in the nervous system of the mouse. Acta Neuropathol., 1984, 63(1), 78-79 (Pubitemid 14157698)
183. Kusuhara, H.; Sugiyama, Y. Active efflux across the blood-brain barrier: role of the solute carrier family. NeuroRx., 2005, 2(1), 73-85. (Pubitemid 40128028)
184. Miller, D.S.; Villalobos, A.R.; Pritchard, J.B. Organic cation transport in rat choroid plexus cells studied by fluorescence microscopy. Am. J. Physiol., 1999, 276(4 Pt 1), C955-68.
185. Sung, J.H.; Yu, K.H.; Park, J.S.; Tsuruo, T.; Kim, D.D.; Shim, C.K.; Chung, S.J. Saturable distribution of tacrine into the striatal extracellular fluid of the rat: evidence of involvement of multiple organic cation transporters in the transport. Drug Metab. Dispos., 2005, 33(3), 440-448
186. Yelin, R.; Schuldiner, S. The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters. FEBS Lett., 1995, 377(2), 201-207 (Pubitemid 26018524)
187. Haberberger, R.V.; Pfeil, U.; Lips, K.S.; Kummer, W. Expression of the high-affinity choline transporter, CHT1, in the neuronal and non-neuronal cholinergic system of human and rat skin. J. Invest. Dermatol., 2002, 119(4), 943-948 (Pubitemid 35340922)
188. Hoffmann, K.; Grafe, F.; Wohlrab, W.; Neubert, R.H.; Brandsch, M. Functional characterization of a high-affinity choline transport system in human keratinocytes. J. Invest. Dermatol., 2002, 119(1), 118-121 (Pubitemid 35304399)
189. Shnitsar, V.; Eckardt, R.; Gupta, S.; Grottker, J.; Muller, G.A.; Koepsell, H.; Burckhardt, G.; Hagos, Y. Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res., 2009, 69(4), 1494-1501
190. Di Virgilio, F.; Ferrari, D.; Adinolfi, E. P2X(7): a growth-promoting receptor-implications for cancer. Purinergic Signal, 2009, 5(2), 251-256
191. Pellegatti, P.; Raffaghello, L.; Bianchi, G.; Piccardi, F.; Pistoia, V.; Di Virgilio, F. Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One, 2008, 3(7), e2599.
192. Li, D.; Zhao, B.; Sim, S.P.; Li, T.K.; Liu, A.; Liu, L.F.; LaVoie, E.J. 2,3-Dimethoxybenzo[i]phenanthridines: topoisomerase I-targeting anticancer agents. Bioorg. Med. Chem., 2003, 11(4), 521-528 (Pubitemid 36132229)
193. Makhey, D.; Li, D.; Zhao, B.; Sim, S.P.; Li, T.K.; Liu, A.; Liu, L.F.; LaVoie, E.J. Substituted benzo[i]phenanthridines as mammalian topoisomerase-targeting agents. Bioorg. Med. Chem., 2003, 11(8), 1809-1820
194. Han, M.H.; Kim, S.O.; Kim, G.Y.; Kwon, T.K.; Choi, B.T.; Lee, W.H.; Choi, Y.H. Induction of apoptosis by sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt. Anticancer Drugs, 2007, 18(8), 913-921
195. Jonker, J.W.; Wagenaar, E.; Mol, C.A.; Buitelaar, M.; Koepsell, H.; Smit, J.W.; Schinkel, A.H. 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), 5471-5477
196. Aleksunes, L.M.; Augustine, L.M.; Scheffer, G.L.; Cherrington, N.J.; Manautou, J.E. Renal xenobiotic transporters are differentially expressed in mice following cisplatin treatment. Toxicology, 2008, 250(2-3), 82-88
197. Gründemann, D.; Hahne, C.; Berkels, R.; Schömig, E. Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J. Pharmacol. Exp. Ther., 2003, 304(2), 810-817 (Pubitemid 36152360)
198. Busch, A.E.; Quester, S.; Ulzheimer, J.C.; Gorboulev, V.; Akhoundova, A.; Waldegger, S.; Lang, F.; Koepsell, H. Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS. Lett., 1996, 395(2-3), 153-156 (Pubitemid 26356174)
199. Kimura, N.; Masuda, S.; Tanihara, Y.; Ueo, H.; Okuda, M.; Katsura, T.; Inui, K. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab. Pharmacokinet., 2005, 20(5), 379-386
200. Wang, D.S.; Jonker, J.W.; Kato, Y.; Kusuhara, H.; Schinkel, A.H.; Sugiyama, Y. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol. Exp. Ther., 2002, 302(2), 510-515 (Pubitemid 34787213)
201. Kimura, N.; Okuda, M.; Inui, K. Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm. Res., 2005, 22(2), 255-259 (Pubitemid 40487209)
202. van Montfoort, J.E.; Muller, M.; Groothuis, G.M.; Meijer, D.K.; Koepsell, H.; Meier, P.J. Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J. Pharmacol. Exp. Ther., 2001, .298(1), 110-115 (Pubitemid 32574516)
203. Martel, F.; Vetter, T.; Russ, H.; Grundemann, D.; Azevedo, I.; Koepsell, H.; Schömig, E. Transport of small organic cations in the rat liver. The role of the organic cation transporter OCT1. Naunyn. Schmiedebergs Arch. Pharmacol., 1996, 354(3), 320-326 (Pubitemid 26284497)
204. Zhang, L.; Schaner, M.E.; Giacomini, K.M. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J. Pharmacol. Exp. Ther., 1998, 286(1), 354-361 (Pubitemid 28318011)