药学学报, 2014, 49(8): 1105-1110
引用本文:
杨媛媛, 马越鸣. 多药及毒素外排转运蛋白研究进展[J]. 药学学报, 2014, 49(8): 1105-1110.
YANG Yuan-yuan, MA Yue-ming. Progress in the study of multidrug and toxin extrusion proteins[J]. Acta Pharmaceutica Sinica, 2014, 49(8): 1105-1110.

多药及毒素外排转运蛋白研究进展
杨媛媛, 马越鸣
上海中医药大学中药学院, 上海 201203
摘要:
多药及毒性化合物外排转运蛋白(MATEs) 在有机阳离子体内转运过程中发挥重要作用,涉及临床上多种常用药物和重要的内源性物质的最终排泄过程。本文对MATEs的发现、分型、基因编码及多态性、体内分布、底物及抑制剂的分类及研究方法等方面的研究进展进行综述,结合实例对研究意义进行分析。
关键词:    外排转运体      多药及毒性化合物外排转运蛋白      研究进展     
Progress in the study of multidrug and toxin extrusion proteins
YANG Yuan-yuan, MA Yue-ming
College of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Abstract:
Mammal multidrug and toxin extrusion proteins (MATEs) play an important role in the transport of organic cations in the body. MATEs mediate the final excretion step for multiple organic cation drug used clinically and important endogenous substances. This article reviews the discovery, type, gene coding and po-lymorphism, body distribution, classification of substrates and inhibitors and their research method of MATEs. The article also discusses the major research significance of MATEs with examples.
Key words:    efflux transporter    mammal multidrug and toxin extrusion proteins    research progress   
收稿日期: 2014-01-20
基金项目: 国家自然科学基金资助项目(81273658);高等学校博士学科点专项科研基金资助项目(20113107110005);“085”一流学科建设科技创新支撑计划:引导创新计划(085ZY1205).
通讯作者: 马越鸣 Tel/Fax:86-21-51322386,E-mail:mayueming_117@126.com
Email: mayueming_117@126.com
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参考文献:
[1] Zhang J, Liu KX. Intestinal absorption and renal excretion mediated by transporters and the relationship with drug-drug interaction [J]. Acta Pharm Sin (药学学报), 2010, 45: 1089-1094.
[2] Sun J, Sun YB, He ZG. Significant role of transporters in drug hepatobiliary transport [J]. Acta Pharm Sin (药学学报), 2005, 40: 680-685.
[3] Gao CY, Chen XY, Zhong DF. Role of transporters in hepatic drug disposition [J]. Acta Pharm Sin (药学学报), 2012, 47: 565-572.
[4] Otsuka M, Matsumoto T, Morimoto R, et al. A human transporter protein that mediates the final excretion step for toxic organic cations [J]. Proc Natl Acad Sci USA, 2005, 102: 17923-17928.
[5] Morita Y, Kodama K, Shiota S, et al. NorM, a putative multidrug efflux protein, of vibrio parahaemolyticus and its homolog in Escherichia coli [J]. Antimicrob Agents Chemother, 1998, 42:1778-1782.
[6] Yonezawa A, Inui Ki. Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics [J]. Br J Pharmacol, 2011, 164: 1817-1825.
[7] Masuda S, Terada T, Yonezawa A, et al. Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2 [J]. J Am Soc Nephrol, 2006, 17: 2127-2135.
[8] Staud F, Cerveny L, Ahmadimoghaddam D, et al. Mul-tidrug and toxin extrusion proteins (MATE/SLC47); role in pharmacokinetics [J]. Int J Biochem Cell Biol, 2013, 45: 2007-2011.
[9] Komatsu T, Hiasa M, Miyaji T, et al. Characterization of the human MATE2 proton-coupled polyspecific organic cation exporter [J]. Int J Biochem Cell Biol, 2011, 43: 913-918.
[10] Ahmadimoghaddam D, Staud F. Transfer of metformin across the rat placenta is mediated by organic cation trans-porter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) protein [J]. Reprod Toxicol, 2013, 39: 17-22.
[11] 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 1 [J]. Biol Reprod, 2013, 88: 1-10.
[12] Damme K, Nies AT, Schaeffeler E, et al. Mammalian MATE (SLC47A) transport proteins: impact on efflux of endogenous substrates and xenobiotics [J]. Drug Metab Rev, 2011, 43: 499-523.
[13] Terada T, Masuda S, Asaka J, et al. Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1 [J]. Pharm Res, 2006, 23: 1696-1701.
[14] Hiasa M, Matsumoto T, Komatsu T, et al. Functional characterization of testis-specific rodent multidrug and toxic compound extrusion 2, a class III MATE-type polyspecific H+/organic cation exporter [J]. Am J Physiol Cell Physiol, 2007, 293: C1437-1444.
[15] Stocker SL, Morrissey KM, Yee SW, et al. The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin [J]. Clin Pharmacol Ther, 2013, 93: 186-194.
[16] Kajiwara M, Terada T, Ogasawara K, et al. Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity [J]. J Hum Genet, 2009, 54: 40-46.
[17] Kajiwara M, Terada T, Asaka J, et al. Critical roles of Sp1 in gene expression of human and rat H+/organic cation antiporter MATE1 [J]. Am J Physiol Renal Physiol, 2007, 293: F1564-F1570.
[18] Tanihara Y, Masuda S, Sato T, et al. Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters [J]. Biochem Pharmacol, 2007, 74: 359-371.
[19] Müller F, König J, Hoier E, et al. Role of organic cation transporter OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2-K for transport and drug interactions of the antiviral lamivudine [J]. Biochem Pharmacol, 2013, 86: 808-815.
[20] Astorga B, Ekins S, Morales M, et al. Molecular determi-nants of ligand selectivity for the human multidrug and toxin extruder proteins MATE1 and MATE2-K [J]. J Pharmacol Exp Ther, 2012, 341: 743-755.
[21] Wittwer MB, Zur AA, Khuri N, et al. Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling [J]. J Med Chem, 2013, 56: 781-795.
[22] Sato T, Masuda S, Yonezawa A, et al. Transcellular trans-port of organic cations in double-transfected MDCK cells expressing human organic cation transporters hOCT1/hMATE1 and hOCT2/hMATE1 [J]. Biochem Pharmacol, 2008, 76: 894-903.
[23] Tsuda M, Terada T, Mizuno T, et al. Targeted disruption of the multidrug and toxin extrusion 1 (mate1) gene in mice reduces renal secretion of metformin [J]. Mol Pharmacol, 2009, 75: 1280-1286.
[24] Toyama K, Yonezawa A, Masuda S, et al. Loss of mul-tidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis [J]. Br J Pharmacol, 2012, 166: 1183-1191.
[25] Ito S, Kusuhara H, Yokochi M, et al. Competitive inhibi-tion 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]. J Pharmacol Exp Ther, 2012, 340: 393-403.
[26] Kusuhara H, Ito S, Kumagai Y, et al. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects [J]. Clin Pharmacol Ther, 2011, 89: 837-844.
[27] Hiasa M, Matsumoto T, Komatsu T, et al. Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations [J]. Am J Physiol Cell Physiol, 2006, 291: C678-686.
[28] Omote H, Hiasa M, Matsumoto T, et al. The MATE pro-teins as fundamental transporters of metabolic and xenobiotic organic cations [J]. Trends Pharmacol Sci, 2006, 27: 587-593.
[29] Nishihara K, Masuda S, Ji L, et al. Pharmacokinetic significance of luminal multidrug and toxin extrusion 1 in chronic renal failure rats [J]. Biochem Pharmacol, 2007, 73: 1482-1490.
[30] Gaowa A, Motohashi H, Katsura T, et al. Effects of metabolic acidosis on expression levels of renal drug transporters [J]. Pharm Res, 2011, 28: 1023-1030.
[31] Grottker J, Rosenberger A, Burckhardt G, et al. Interaction of human multidrug and toxin extrusion 1 (MATE1) trans-porter with antineoplastic agents [J]. Drug Metab Drug Interact, 2011, 26: 181-189.
[32] Ahmadimoghaddam D, Hofman J, Zemankova L, et al. Synchronized activity of organic cation transporter 3 (Oct3/Slc22a3) and multidrug and toxin extrusion 1 (Mate1/Slc47a1) transporter in transplacental passage of MPP+ in rat [J]. Toxicol Sci, 2012, 128: 471-481.
[33] Yokoo S, Yonezawa A, Masuda S, et al. Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity [J]. Biochem Pharmacol, 2007, 74: 477-487.
[34] Grun B, Kiessling MK, Burhenne J, et al. Trimethoprim-metformin interaction and its genetic modulation by OCT2 and MATE1 [J]. Br J Clin Pharmacol, 2013, 76: 787-796.
[35] Li Q, Guo D, Dong Z, et al. Ondansetron can enhance cisplatin-induced nephrotoxicity via inhibition of multiple toxin and extrusion proteins (MATEs) [J]. Toxicol Appl Pharmacol, 2013, 273: 100-109.
[36] Becker ML, Visser LE, van Schaik RH, et al. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study [J]. Diabetes, 2009, 58: 745-749.