Research progress of organic cation transporters

Abstract

Abstract: Nowadays, more and more attentions have been attached to the importance of organic cation transporters (OCTs). OCTs has involved in the transmembrane transport of numerous significant endogenous and exogenous substances including many clinical drugs. Therefore, recent progress on the interactions between OCTs and these substances, the regulation of OCTs expression and the influence of OCTs polymorphism are reviewed in this paper.

Key words: Organic cation transporters, Drug-drug interactions, Gene polymorphism

CLC Number:

R969.1

LI Xiao-nan, CHEN Jia-yin, SUN Xiao-lin, ZHANG Yong-jie, WANG Chun-feng, WEN Yan-li, WANG Sui-loU, CHEN Xi-jing. Research progress of organic cation transporters[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(8): 954-960.

References

[1] Nies AT, Koepsell H, Damme K, et al. Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy [J]. Handb Exp Pharmacol, 2011, (201): 105-167.
[2] Giacomini KM, Huang SM, Tweedie DJ, et al. Membrane transporters in drug development [J]. Nat Rev Drug Discov, 2010, 9: 215-236.
[3] Zhu HJ, Appel DI, Gründemann D, et al. Evaluation of organic cation transporter 3 (SLC22A3) inhibition as a potential mechanism of antidepressant action [J]. Pharmacol Res, 2012, 65(4): 491-496.
[4] Feng N, Lowry CA, Lukkes JL, et al. Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint [J]. Brain Res, 2010, 1326: 105-113.
[5] Tachikawa M, Hosoya K. Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders [J]. Fluids Barriers CNS, 2011, 8(1): 13.
[6] Sala-Rabanal M, Li DC, Dake GR, et al. Polyamine transport by the polyspecific organic cation transporters OCT1, OCT2 and OCT3 [J]. Mol Pharmaceutics, 2013, 10(4): 1450-1458.
[7] Taubert D, Grimberg G, Stenzel W, et al. Identification of the endogenous key substrates of the human organic cation transporter OCT2 and their implication in function of dopaminergic neurons [J]. PLoS One, 2007, 2(4): e385.
[8] Zhang S, Lovejoy KS, Shima JE, et al. Organic cation transporters are determinants of oxaliplatin cytotoxicity [J]. Cancer Res, 2006, 66 (17): 8847-8857.
[9] More SS, Li S, Yee SW, et al. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue [J]. Mol Cancer Ther, 2010, 9(4): 1058-1069.
[10] Ciarimboli G, Deuster D, Knief A, et al. Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a target for protective interventions [J]. Am J Pathol, 2010, 176(3): 1169-1180.
[11] Bachmakov I, Glaeser H, Endress B, et al. Interaction of beta-blockers with the renal uptake transporter OCT2 [J]. Diabetes Obes Metab, 2009, 11(11): 1080-1083.
[12] Nies AT, Hofmann U, Resch C, et al. Proton pump inhibitors inhibit metformin uptake by organic cation transporters (OCTs) [J]. PLoS One, 2011, 6(7): e22163.
[13] Minematsu T, Giacomini KM. Interactions of tyrosine kinase inhibitors with organic cation transporters, OCTs, and multidrug and toxic compound extrusion proteins, MATEs [J]. Mol Cancer Ther, 2011, 10(3): 531-539.
[14] Kimura N, Masuda S, Katsura T, et al. Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2 [J]. Biochem Pharmacol, 2009, 77(8): 1429-1436.
[15] Bacq A, Balasse L, Biala G, et al. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response [J]. Mol Psychiatry, 2012, 17(9): 926-939.
[16] Horton RE, Apple DM, Owens WA, et al. Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression [J]. J Neurosci, 2013, 33(25): 10534-10543.
[17] Mamlouk M, Young PM, Bebawy M, et al. Salbutamol sulfate absorption across Calu-3 bronchial epithelia cell monolayer is inhibited in the presence of common anionic NSAIDs [J]. J Asthma, 2013, 50(4): 334-341.
[18] Nakanishi T, Haruta T, Shirasaka Y, et al. Organic cation transporter-mediated renal secretion of ipratropium and tiotropium in rats and humans [J]. Drug Metab Dispos, 2011, 39(1): 117-122.
[19] Mukherjee M, Pritchard DI, Bosquillon C. Evaluation of air-interfaced Calu-3 cell layers for investigation of inhaled drug interactions with organic cation transporters in vitro[J]. Int J Pharm, 2012, 426(1/2): 7-14.
[20] Nies AT, Koepsell H, Winter S, et al. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver [J]. Hepatology, 2009, 50(4): 1227-1240.
[21] Ahmadimoghaddam D, Zemankova L, Nachtigal P, et al. Organic cation transporter 3 (OCT3/ SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter in the placenta and fetal tissues: expression profile and fetus protective role at different stages of gestation [J]. Biol Reprod, 2013, 88(3): 55.
[22] Kurata T, Muraki Y, Mizutani H, et al. Elevated systemic elimination of cimetidine in rats with acute biliary obstruction: the role of renal organic cation transporter OCT2 [J]. Drug Metab Pharmacokinet, 2010, 25(4): 328-334.
[23] Komazawa H, Yamaguchi H, Hidaka K, et al. Renal uptake of substrates for organic anion transporters Oat1 and Oat3 and organic cation transporters Oct1 and Oct2 is altered in rats with adenine-induced chronic renal failure [J]. J Pharm Sci, 2013, 102(3): 1086-1094.
[24] Heemskerk S, Wouterse AC, Russel FG, et al. Nitric oxide down-regulates the expression of organic cation transporters (OCT) 1 and 2 in rat kidney during endotoxemia [J]. Eur J Pharmacol, 2008, 584(2/3): 390-397.
[25] Soodvilai S, Chatsudthipong A, Chatsudthipong V. Role of MAPK and PKA in regulation of rbOCT2-mediated renal organic cation transport [J]. Am J Physiol Renal Physiol, 2007, 293(1): F21-F27.
[26] Nie W, Sweetser S, Rinella M, et al. Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-alpha and -gamma [J]. Am J Physiol Gastrointest Liver Physiol, 2005, 288(2): G207-G212.
[27] Meetam P, Srimaroeng C, Soodvilai S, et al. Regulatory role of testosterone in organic cation transport: in vivo and in vitro studies [J]. Biol Pharm Bull, 2009, 32(6): 982-987.
[28] Heise M, Lautem A, Knapstein J, et al. Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance [J]. BMC Cancer, 2012, 12: 109.
[29] Cho SK, Yoon JS, Lee MG, et al. Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants [J]. Clin Pharmacol Ther, 2011, 89(3): 416-421.
[30] Jang EH, Kim HK, Park CS, et al. Increased expression of hepatic organic cation transporter 1 and hepatic distribution of metformin in high-fat diet-induced obese mice [J]. Drug Metab Pharmacokinet, 2010, 25(4): 392-397.
[31] Moreno-Navarrete JM, Ortega FJ, Rodríguez-Hermosa JI, et al. OCT1 expression in adipocytes could contribute to increased metformin action in obese subjects [J]. Diabetes, 2011, 60(1): 168-176.
[32] Patel H, Younis RH, Ord RA, et al. Differential expression of organic cation transporter OCT-3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin [J]. J Oral Pathol Med, 2013, 42(3): 250-256.
[33] Asavapanumas N, Kittayaruksakul S, Meetam P, et al. Fenofibrate down-regulates renal OCT2-mediated organic cation transporter via PPARα-independent pathways [J]. Drug Metab Pharmacokinet, 2012, 27(5): 513-519.
[34] Giannoudis A, Wang L, Jorgensen AL, et al. The hOCT1 SNPs M420del and M408V alter imatinib uptake and M420del modifies clinical outcome in imatinib-treated chronic myeloid leukemia [J]. Blood, 2013, 121(4): 628-637.
[35] Becker ML, Visser LE, van Schaik RH, et al. OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users [J]. Neurogenetics, 2011, 12(1): 79-82.
[36] Becker ML, Visser LE, van Schaik RH, et al. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus [J]. Pharmacogenomics J, 2009, 9(4): 242-247.
[37] Ahlin G, Chen L, Lazorova L, et al. Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions [J]. Pharmacogenomics J, 2011, 11(6): 400-411.
[38] Gambineri A, Tomassoni F, Gasparini DI, et al. Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome [J]. J Clin Endocrinol Metab, 2010, 95(10): E204-E208.
[39] Zolk O, Solbach TF, König J, et al. Functional characterization of the human organic cation transporter 2 variant p.270Ala >Ser [J]. Drug Metab Dispos, 2009, 37(6): 1312-1318.
[40] Song IS, Shin HJ, Shin JG. Genetic variants of organic cation transporter 2 (OCT2) significantly reduce metformin uptake in oocytes [J]. Xenobiotica, 2008, 38(9): 1252-1262.
[41] Li Q, Liu F, Zheng TS, et al. SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin [J]. Acta Pharmacol Sin. 2010, 31(2): 184-190.
[42] Choi MK, Song IS. Genetic variants of organic cation transporter 1 (OCT1) and OCT2 significantly reduce lamivudine uptake [J]. Biopharm Drug Dispos, 2012, 33(3): 170-178.
[43] Chen L, Pawlikowski B, Schlessinger A, et al. Role of organic cation transporter 3 (SLC22A3) and its missense variants in the pharmacologic action of metformin [J]. Pharmacogenet Genomics, 2010, 20(11): 687-699.
[44] Park TJ, Kim JH, Bae JS, et al. Possible Association of SLC22A2 Polymorphisms with Aspirin-Intolerant Asthma [J]. Int Arch Allergy Immunol, 2011, 155(4): 395-402.
[45] Zhang J, Zhou W. Ameliorative effects of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity in Chinese cancer patients [J]. Food Chem Toxicol, 2012, 50(7): 2289-2293.