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Drug Transporters


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Ito S, Kusuhara H, Kuroiwa Y, Wu C, Moriyama Y, Inoue K, Kondo T, Yuasa H, Nakayama H, Horita S, Sugiyama Y. Potent and specific inhibition of mMate1‐mediated efflux of type I organic cations in the liver and kidney by pyrimethamine. J Pharmacol Exp Ther 2010; 333 (1):341–350.

      53 [53] Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM. Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem 2013; 56 (3):781–795.

      54 [54] Astorga B, Ekins S, Morales M, Wright SH. Molecular determinants of ligand selectivity for the human multidrug and toxin extruder proteins MATE1 and MATE2‐K. J Pharmacol Exp Ther 2012; 341 (3):743–755.

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      56 [56] Belzer M, Morales M, Jagadish B, Mash EA, Wright SH. Substrate‐dependent ligand inhibition of the human organic cation transporter OCT2. J Pharmacol Exp Ther 2013; 346 (2):300–10.

      57 [57] Hacker K, Maas R, Kornhuber J, Fromm MF, Zolk O. Substrate‐dependent inhibition of the human organic cation transporter OCT2: a comparison of metformin with experimental substrates. PLoS One 2015; 10 (9):e0136451.

      58 [58] Martínez‐Guerrero LJ, Wright SH. Substrate‐dependent inhibition of human MATE1 by cationic ionic liquids. J Pharmacol Exp Ther 2013; 346 (3):495–503.

      59 [59] Martínez‐Guerrero LJ, Morales M, Ekins S, Wright SH. Lack of influence of substrate on ligand interaction with the human multidrug and toxin extruder, MATE1. Mol Pharmacol 2016; 90 (3):254–64.

      60 [60] Yin J, Duan H, Wang J. Impact of substrate‐dependent inhibition on renal organic cation transporters hOCT2 and hMATE1/2‐K‐mediated drug transport and intracellular accumulation. J Pharmacol Exp Ther 2016; 359 (3):401–410.

      61 [61] Zhang X, Wright SH. MATE1 has an external COOH terminus, consistent with a 13‐helix topology. Am J Physiol Renal Physiol 2009; 297 (2):F263–F271.

      62 [62] Kobara A, Hiasa M, Matsumoto T, Otsuka M, Omote H, Moriyama Y. A novel variant of mouse MATE‐1 H+/organic cation antiporter with a long hydrophobic tail. Arch Biochem Biophys. 2008; 469 (2):195–199.

      63 [63] Zhang X, He X, Baker J, Tama F, Chang G, Wright SH. Twelve transmembrane helices form the functional core of mammalian MATE1 (multidrug and toxin extruder 1) protein. J Biol Chem 2012; 287 (33):27971–27982.

      64 [64] He X, Szewczyk P, Karyakin A, Evin M, Hong WX, Zhang Q, Chang G. Structure of a cation‐bound multidrug and toxic compound extrusion transporter. Nature 2010; 467 (7318):991–994.

      65 [65] Miyauchi H, Moriyama S, Kusakizako T, Kumazaki K, Nakane T, Yamashita K, Hirata K, Dohmae N, Nishizawa T, Ito K, Miyaji T, Moriyama Y, Ishitani R, Nureki O. Structural basis for xenobiotic extrusion by eukaryotic MATE transporter. Nat Commun 2017; 8 (1):1633.

      66 [66] Asaka J, Terada T, Tsuda M, Katsura T, Inui K. Identification of essential histidine and cysteine residues of the H+/organic cation antiporter multidrug and toxin extrusion (MATE). Mol Pharmacol 2007; 71 (6):1487–93.

      67 [67] Matsumoto T, Kanamoto T, Otsuka M, Omote H, Moriyama Y. Role of glutamate residues in substrate recognition by human MATE1 polyspecific H+/organic cation exporter. Am J Physiol Cell Physiol 2008; 294 (4):C1074–8.

      68 [68] Kajiwara M, Terada T, Asaka J, Ogasawara K, Katsura T, Ogawa O, Fukatsu A, Doi T, Inui K. Critical roles of Sp1 in gene expression of human and rat H+/organic cation antiporter MATE1. Am J Physiol Renal Physiol 2007; 293 (5):F1564–F1570.

      69 [69] Martovetsky G, Tee JB, Nigam SK. Hepatocyte nuclear factors 4α and 1α regulate kidney developmental expression of drug‐metabolizing enzymes and drug transporters. Mol Pharmacol 2013; 84 (6):808–823.

      70 [70] Fukuda Y, Kaishima M, Ohnishi T, Tohyama K, Chisaki I, Nakayama Y, Ogasawara‐Shimizu M, Kawamata Y. Fluid shear stress stimulates MATE2‐K expression via Nrf2 pathway activation. Biochem Biophys Res Commun 2017; 484 (2):358–364.

      71 [71] Atilano‐Roque A, Aleksunes LM, Joy MS. Bardoxolone methyl modulates efflux transporter and detoxifying enzyme expression in cisplatin‐induced kidney cell injury. Toxicol Lett 2016; 259:52–59.

      72 [72] Arruda AC, Perilhão MS, Santos WA, Gregnani MF, Budu A, Neto JCR, Estrela GR, Araujo RC. PPARα‐dependent modulation by metformin of the expression of OCT‐2 and MATE‐1 in the kidney of mice. Molecules 2020; 25 (2):392.

      73 [73] Ferrigno A, Di Pasqua LG, Berardo C, Siciliano V, Rizzo V, Adorini L, Richelmi P, Vairetti M. The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE‐1 during hepatic ischemia/reperfusion injury. PLoS One 2018; 13 (1):e0191430.

      74 [74] Kantauskaite M, Hucke A, Reike M, Ahmed Eltayeb S, Xiao C, Barz V, Ciarimboli G. Rapid regulation of human multidrug and extrusion transporters hMATE1 and hMATE2K. Int J Mol Sci 2020; 21 (14):5157.

      75 [75] Xu YJ, Wang Y, Lu YF, Xu SF, Wu Q, Liu J. Age‐associated differences in transporter gene expression in kidneys of male rats. Mol Med Rep 2017; 15 (1):474–482.

      76 [76] Wen J, Zeng M, Shu Y, Guo D, Sun Y, Guo Z, Wang Y, Liu Z, Zhou H, Zhang W. Aging increases the susceptibility of cisplatin‐induced nephrotoxicity. Age (Dordr) 2015; 37 (6):112.

      77 [77] Meetam P, Srimaroeng C, Soodvilai S, Chatsudthipong V. Role of estrogen in renal handling of organic cation, tetraethylammonium: in vivo and in vitro studies. Biol Pharm Bull 2009; 32 (12):1968–72.

      78 [78] He R, Ai L, Zhang D, Wan L, Zheng T, Yin J, Lu H, Lu J, Lu F, Liu F, Jia W. Different effect of testosterone and oestrogen on urinary excretion of metformin via regulating OCTs and MATEs expression in the kidney of mice. J Cell Mol Med 2016; 20 (12):2309–2317.

      79 [79] Lee N, Hebert MF, Prasad B, Easterling TR, Kelly EJ, Unadkat JD, Wang J. Effect of gestational age on mRNA and protein expression of polyspecific organic cation transporters during pregnancy. Drug Metab Dispos 2013; 41 (12):2225–2232.

      80 [80] Yacovino LL, Gibson CJ, Aleksunes LM. Down‐regulation of brush border efflux transporter expression in the kidneys of pregnant mice. Drug Metab Dispos 2013; 41 (2):320–325.

      81 [81] Bergagnini‐Kolev MC, Hebert MF, Easterling TR, Lin YS. Pregnancy increases the renal secretion of N(1)‐methylnicotinamide, an endogenous probe for renal cation transporters, in patients prescribed metformin. Drug Metab Dispos 2017; 45 (3):325–329.

      82 [82] Nishihara K, Masuda S, Ji L, Katsura T, Inui K. Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure rats. Biochem Pharmacol. 2007; 73 (9):1482–1490.

      83 [83] Matsuzaki T, Morisaki T, Sugimoto W, Yokoo K, Sato D, Nonoguchi H, Tomita K, Terada T, Inui K, Hamada A, Saito H. Altered pharmacokinetics of cationic drugs caused by down‐regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion‐induced acute kidney injury. Drug Metab Dispos. 2008; 36 (4):649–654.

      84 [84] Morisaki T, Matsuzaki T, Yokoo K, Kusumoto M, Iwata K, Hamada A, Saito H. Regulation of renal organic ion transporters in cisplatin‐induced acute kidney injury and uremia in rats. Pharm Res. 2008; 25 (11):2526–2533.

      85 [85] Clarke JD, Dzierlenga AL, Nelson NR, Li H, Werts S, Goedken MJ, Cherrington NJ. Mechanism of altered metformin distribution in nonalcoholic steatohepatitis. Diabetes 2015; 64 (9):3305–3313.

      86 [86] Schiöth HB, Boström A, Murphy SK, Erhart W, Hampe J, Moylan C, Mwinyi J. A targeted analysis reveals relevant shifts in the methylation and transcription of genes responsible for bile acid homeostasis and drug metabolism in non‐alcoholic fatty liver disease. BMC Genomics 2016; 17:462.

      87 [87] García‐Calzón S, Perfilyev A, Männistö V, de Mello VD, Nilsson E, Pihlajamäki J, Ling C. Diabetes medication associates with DNA methylation of metformin transporter genes in the human