Multidrug resistance-associated proteins 3, 4, and 5

被引:227
作者
Borst, Piet
de Wolf, Cornelia
de Wetering, Koen van
机构
[1] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
[2] Netherlands Canc Inst, Ctr Genet Mol, NL-1066 CX Amsterdam, Netherlands
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2007年 / 453卷 / 05期
关键词
6MP; 6-mercaptopurine; 6TG; 6-thioguanine; 5-FudR; 5-fluorodeoxyuridine; ABC; ATP-binding cassette; BCRP; breast cancer resistance;
D O I
10.1007/s00424-006-0054-9
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We summarize in this paper the recently published results on multidrug resistance-associated proteins 3, 4, and 5 (MRPs 3-5). MRP3 can transport organic compounds conjugated to glutathione, sulfate, or glucuronate, such as estradiol-17 beta-glucuronide, bilirubin-glucuronides, and etoposide-glucuronide, and also bile salts and methotrexate. Studies in knockout mice have shown that Mrp3 contributes to the transport of morphine-3-glucuronide and acetaminophen-glucuronide from the liver into blood. There is no evidence for a major role of MRP3 in bile salt metabolism, at least in mice. The function of MRP3 in other tissues, notably the gut and the adrenal cortex, remains to be defined. MRP4 and MRP5 have attracted attention by their ability to transport cyclic nucleotides and many nucleotide analogs. The initial reports that MRP4 and 5 can transport cGMP with mu M affinity have not been confirmed in recent work and the physiological importance of cyclic nucleotide transport by MRP4 and 5 remains to be determined. Transfected cells containing high concentrations of MRP4 and 5 are moderately resistant to base, nucleoside, and nucleotide analogs. The affinity of both transporters for nucleotide analogs is low (K-m around 1 mM) and there is no evidence that the transport of these compounds results in resistance in vivo. The physiological function of MRP4 and 5 remains to be found.
引用
收藏
页码:661 / 673
页数:13
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