Document Detail


Multidrug resistance-associated proteins 3, 4, and 5.
MedLine Citation:
PMID:  16586096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-17beta-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 microM 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.
Authors:
Piet Borst; Cornelia de Wolf; Koen van de Wetering
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2006-04-04
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  453     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-31     Completed Date:  2007-08-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  661-73     Citation Subset:  IM    
Affiliation:
Division of Molecular Biology and Center of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. p.borst@nki.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclic GMP / metabolism
Drug Resistance, Neoplasm
Humans
Multidrug Resistance-Associated Proteins / antagonists & inhibitors,  biosynthesis,  genetics,  physiology*
Substrate Specificity
Tissue Distribution
Chemical
Reg. No./Substance:
0/ABCC4 protein, human; 0/ABCC5 protein, human; 0/Multidrug Resistance-Associated Proteins; 0/multidrug resistance-associated protein 3; 7665-99-8/Cyclic GMP

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