1,354
Views
73
CrossRef citations to date
0
Altmetric
Review

Role of organic cation transporters in drug–drug interaction

Bibliography

  • Gründemann D, Gorboulev V, Gambaryan S, et al. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 1994;372:549–52
  • Koepsell H. The SLC22 family with transporters of organic cations, anions and zwitterions. Mol Aspects Med 2013;34:413–35
  • Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 2007;24:1227–51
  • Nies AT, Koepsell H, Damme K, Schwab M. Organic cation transporters (OCTs,MATEs), in vitro and in vivo evidence for the importance in drug therapy. Handb Exp Pharmacol 2010;201:105–67
  • Rizwan AN, Burckhardt G. Organic anion transporters of the SLC22 family: biopharmaceutical, physiological, and pathological roles. Pharm Res 2007;24:450–70
  • Koepsell H, Schmitt BM, Gorboulev V. Organic cation transporters. Rev Physiol Biochem Pharmacol 2003;150:36–90
  • Koepsell H. Substrate recognition and translocation by polyspecific organic cation transporters. Biol Chem 2011;392:95–101
  • Keller T, Egenberger B, Gorboulev V, et al. The large extracellular loop of organic cation transporter 1 influences substrate affinity and is pivotal for oligomerization. J Biol Chem 2011;286:37874–86
  • Brast S, Grabner A, Sucic S, et al. The cysteines of the extracellular loop are crucial for trafficking of human organic cation transporter 2 to the plasma membrane and are involved in oligomerization. FASEB J 2012;26:976–86
  • Popp C, Gorboulev V, Müller TD, et al. 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;67:1600–11
  • Huang Y, Lemieux MJ, Song J, et al. Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli. Science 2003;301:616–20
  • Abramson J, Smirnova I, Kasho V, et al. Structure and mechanism of the lactose permease of Escherichia coli. Science 2003;301:610–15
  • Abramson J, Smirnova I, Kasho V, et al. The lactose permease of Escherichia coli: overall structure, the sugar-binding site and the alternating access model for transport. FEBS Lett 2003;555:96–101
  • Gorbunov D, Gorboulev V, Shatskaya N, et al. 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;73:50–61
  • Volk C, Gorboulev V, Kotzsch A, et al. Five amino acids in the innermost cavity of the substrate binding cleft of organic cation transporter 1 interact with extracellular and intracellular corticosterone. Mol Pharmacol 2009;76:275–89
  • Arndt P, Volk C, Gorboulev V, et al. Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. Am J Physiol Renal Physiol 2001;281:F454–68
  • Chen R, Jonker JW, Nelson JA. Renal organic cation and nucleoside transport. Biochem Pharmacol 2002;64:185–90
  • Chen L, Shu Y, Liang X, et al. OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. Proc Natl Acad Sci U S A 2014;111:9983–8
  • Boxberger KH, Hagenbuch B, Lampe JN. Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated neurotransmitter uptake. Drug Metab Dispos 2014;42:990–5
  • Kato K, Mori H, Kito T, et al. Investigation of endogenous compounds for assessing the drug interactions in the urinary excretion involving multidrug and toxin extrusion proteins. Pharm Res 2014;31:136–47
  • Muller F, Pontones CA, Renner B, et al. N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction. Eur J Clin Pharmacol 2015;71:85–94
  • Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet 2005;20:452–77
  • Han TK, Everett RS, Proctor WR, et al. Organic cation transporter 1 (OCT1/mOct1) is localized in the apical membrane of Caco-2 cell monolayers and enterocytes. Mol Pharmacol 2013;84:182–9
  • Koepsell H. Organic cation transporters in intestine, kidney, liver, and brain. Annu Rev Physiol 1998;60:243–66
  • Han TK, Proctor WR, Costales CL, et al. Four cation-selective transporters contribute to apical uptake and accumulation of metformin in Caco-2 cell monolayers. J Pharmacol Exp Ther 2015;352:519–28
  • Groer C, Bruck S, Lai Y, et al. LC-MS/MS-based quantification of clinically relevant intestinal uptake and efflux transporter proteins. J Pharm Biomed Anal 2013;85:253–61
  • Traiffort E, Ruat M, O’Regan S, Meunier FM. Molecular characterization of the family of choline transporter-like proteins and their splice variants. J Neurochem 2005;92:1116–25
  • Said HM, Balamurugan K, Subramanian VS, Marchant JS. Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine. Am J Physiol Gastrointest Liver Physiol 2004;286:G491–8
  • Engel K, Zhou M, Wang J. Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem 2004;279:50042–9
  • Shu Y, Sheardown SA, Brown C, et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007;117:1422–31
  • Koepsell H, Gorboulev V, Arndt P. Molecular pharmacology of organic cation transporters in kidney. J Membrane Biol 1999;167:103–17
  • Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci 2006;27:425–46
  • Tzvetkov MV, Vormfelde SV, Balen D, et al. The Effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther 2009;86:299–306
  • Urakami Y, Kimura N, Okuda M, Inui K-I. Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney. Pharm Res 2004;21:976–81
  • Kastrup J, Petersen P, Bartram R, Hansen JM. The effect of trimethoprim on serum creatinine. Br J Urol 1985;57:265–8
  • Naderer O, Nafziger AN, Bertino JSJr. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrob Agents Chemother 1997;41:2466–70
  • Myre SA, McCann J, First MR, Cluxton RJJr. Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers. Ther Drug Monit 1987;9:161–5
  • van Acker BA, Koomen GC, Koopman MG, et al. Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate. Lancet 1992;340:1326–9
  • Berglund F, Killander J, Pompeius R. Effect of trimethoprim-sulfamethoxazole on the renal excretion of creatinine in man. J Urol 1975;114:802–8
  • Gorboulev V, Ulzheimer JC, Akhoundova A, et al. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol 1997;16:871–81
  • Schophuizen CM, Wilmer MJ, Jansen J, et al. Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter. Pflugers Arch 2013;465:1701–14
  • Eisenhofer G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther 2001;91:35–62
  • Busch AE, Karbach U, Miska D, et al. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol 1998;54:342–52
  • Busch AE, Quester S, Ulzheimer JC, et al. Monoamine neurotransmitter transport mediated by the polyspecific cation transporter rOCT1. FEBS Lett 1996;395:153–6
  • Breidert T, Spitzenberger F, Gründemann D, et al. Catecholamine transport by the organic transporter type 1 (OCT1). 1998;125:218–24
  • Lin C-J, Tai Y, Huang M-T, et al. Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood-brain barrier and MPTP-induced dopaminergic toxicity in rodents. J Neurochem 2010;114:717–27
  • Wu KC, Lu YH, Peng YH, et al. Decreased expression of organic cation transporters, Oct1 and Oct2, in brain microvessels and its implication to MPTP-induced dopaminergic toxicity in aged mice. J Cereb Blood Flow Metab 2015;35:37–47
  • Bacq A, Balasse L, Biala G, et al. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry 2012;17:926–39
  • Amphoux A, Vialou V, Drescher E, et al. Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology 2006;50:941–52
  • Nakata T, Matsui T, Kobayashi K, et al. Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline transporter, is preferentially enriched on synaptic vesicles in cholinergic neurons. Neuroscience 2013;252:212–21
  • Sweet DH, Miller DS, Pritchard JB. Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J Biol Chem 2001;276:41611–19
  • Vialou V, Balasse L, Callebert J, et al. Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice. J Neurochem 2008;106:1471–82
  • Schmitt A, Mossner R, Gossmann A, et al. Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice. J Neurosci Res 2003;71:701–9
  • Cui M, Aras R, Christian WV, et al. The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci USA 2009;106:8043–8
  • Wang K, Sun S, Li L, et al. Involvement of organic cation transporter 2 inhibition in potential mechanisms of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry 2014;53:90–8
  • Haenisch B, Drescher E, Thiemer L, et al. Interaction of antidepressant and antipsychotic drugs with the human organic cation transporters hOCT1, hOCT2 and hOCT3. Naunyn Schmiedebergs Arch Pharmacol 2012;385:1017–23
  • Courousse T, Gautron S. Role of organic cation transporters (OCTs) in the brain. Pharmacol Ther 2015;146:94–103
  • Rappold PM, Cui M, Chesser AS, et al. Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc Natl Acad Sci USA 2011;108:20766–71
  • Wultsch T, Grimberg G, Schmitt A, et al. Decreased anxiety in mice lacking the organic cation transporter 3. J Neural Transm 2009;116:689–97
  • Baganz NL, Horton RE, Calderon AS, 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;105:18976–81
  • Kitaichi K, Fukuda M, Nakayama H, et al. Behavioral changes following antisense oligonucleotide-induced reduction of organic cation transporter-3 in mice. Neurosci Lett 2005;382:195–200
  • Courousse T, Bacq A, Belzung C, et al. Brain organic cation transporter 2 controls response and vulnerability to stress and GSK3beta signaling. Mol Psychiatry 2015;20:889–900
  • Volk C, Gorboulev V, Budiman T, et al. Different affinities of inhibitors to the outwardly and inwardly directed substrate binding site of organic cation transporter 2. Mol Pharmacol 2003;64:1037–47
  • Schmitt BM, Koepsell H. Alkali cation binding and permeation in the rat organic cation transporter rOCT2. J Biol Chem 2005;280:24481–90
  • 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;275:29413–20
  • Keller T, Elfeber M, Gorboulev V, et al. Purification and functional reconstitution of the rat organic cation transporter OCT1. Biochemistry 2005;44:12253–63
  • Raschle T, Hiller S, Yu TY, et al. Structural and functional characterization of the integral membrane protein VDAC-1 in lipid bilayer nanodiscs. J Am Chem Soc 2009;131:17777–9
  • Gorboulev V, Volk C, Arndt P, et al. Selectivity of the polyspecific cation transporter rOCT1 is changed by mutation of aspartate 475 to glutamate. Mol Pharmacol 1999;56:1254–61
  • Thevenod F, Ciarimboli G, Leistner M, 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;10:3045–56
  • Belzer M, Morales M, Jagadish B, et al. Substrate-dependent ligand inhibition of the human organic cation transporter OCT2. J Pharmacol Exp Ther 2013;346:300–10
  • Minuesa G, Volk C, Molina-Arcas M, et al. Transport of lamivudine [(-)-b-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;329:252–61
  • Ciarimboli G, Koepsell H, Iordanova M, et al. Individual PKC-phosphorylation sites in organic cation transporter 1 determine substrate selectivity and transport regulation. J Am Soc Nephrol 2005;16:1562–70
  • Kerb R, Brinkmann U, Chatskaia N, et al. Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. Pharmacogenetics 2002;12:591–5
  • Wang ZJ, Yin OQ, Tomlinson B, Chow MS. OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine. Pharmacogenet Genomics 2008;18:637–45
  • Choi MK, Song IS. Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake. Biopharm Drug Dispos 2012;33:170–8
  • Ahlin G, Chen L, Lazorova L, et al. Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions. Pharmacogenomics J 2011;11:400–11
  • Moss DM, Liptrott NJ, Siccardi M, Owen A. Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Front Pharmacol 2015;6:78
  • dos Santos Pereira JN, Tadjerpisheh S, Abu AM, et al. The poorly membrane permeable antipsychotic drugs amisulpride and sulpiride are substrates of the organic cation transporters from the SLC22 family. AAPS J 2014;16:1247–58
  • Shen H, Yang Z, Zhao W, et al. Assessment of vandetanib as an inhibitor of various human renal transporters: inhibition of multidrug and toxin extrusion as a possible mechanism leading to decreased cisplatin and creatinine clearance. Drug Metab Dispos 2013;41:2095–103
  • Hendrickx R, Johansson JG, Lohmann C, et al. Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem 2013;56:7232–42
  • Salomon JJ, Hagos Y, Petzke S, et al. Beta-2 adrenergic agonists are substrates and inhibitors of human organic cation transporter 1. Mol Pharm 2015; In press
  • Minematsu T, Giacomini KM. Interactions of tyrosine kinase inhibitors with organic cation transporters and multidrug and toxic compound extrusion proteins. Mol Cancer Ther 2011;10:531–9
  • Johnston RA, Rawling T, Chan T, et al. Selective inhibition of human solute carrier transporters by multikinase inhibitors. Drug Metab Dispos 2014;42:1851–7
  • Li X, Sun X, Chen J, et al. Investigation of the role of organic cation transporter 2 (OCT2) in the renal transport of guanfacine, a selective alpha2A-adrenoreceptor agonist. Xenobiotica 2015;45:88–94
  • Moreno-Navarrete JM, Ortega FJ, Rodriguez-Hermosa JI, et al. OCT1 Expression in adipocytes could contribute to increased metformin action in obese subjects. Diabetes 2011;60:168–76
  • Tzvetkov MV, dos Santos Pereira JN, Meineke I, et al. Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochem Pharmacol 2013;86:666–78
  • Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med 2002;137:25–33
  • Gong L, Goswami S, Giacomini KM, et al. Metformin pathways: pharmacokinetics and pharmacodynamics. Pharmacogenet Genomics 2012;22:820–7
  • Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011;50:81–98
  • Song IS, Shin HJ, Shim EJ, et al. Genetic variants of the organic cation transporter 2 influence the disposition of metformin. Clin Pharmacol Ther 2008;84:559–62
  • Cho SK, Kim CO, Park ES, Chung JY. Verapamil decreases the glucose-lowering effect of metformin in healthy volunteers. Br J Clin Pharmacol 2014;78:1426–32
  • Grun B, Kiessling MK, Burhenne J, et al. Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 transporters. Br J Clin Pharmacol 2013;76:787–96
  • Kim A, Chung I, Yoon SH, et al. Effects of proton pump inhibitors on metformin pharmacokinetics and pharmacodynamics. Drug Metab Dispos 2014;42:1174–9
  • Ito S, Kusuhara H, Yokochi M, et al. Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther 2012;340:393–403
  • Johansson S, Read J, Oliver S, et al. Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. Clin Pharmacokinet 2014;53:837–47
  • Sprowl JA, Ness RA, Sparreboom A. Polymorphic transporters and platinum pharmacodynamics. Drug Metab Pharmacokinet 2013;28:19–27
  • Giacomini KM, Huang S-M, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov 2010;9:215–36
  • Arimany-Nardi C, Errasti-Murugarren E, Minuesa G, et al. Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors. Br J Pharmacol 2014;171:3868–80

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.