Linked Life Data

12704183

Source:http://linkedlifedata.com/resource/pubmed/id/12704183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2003-6-23
pubmed:abstractText
The multidrug resistance proteins MRP2 (ABCC2) and MRP3 (ABCC3) are key primary active transporters involved in anionic conjugate and drug extrusion from the human liver. The major physiological role of MRP2 is to transport conjugated metabolites into the bile canaliculus, whereas MRP3 is localized in the basolateral membrane of the hepatocytes and transports similar metabolites back to the bloodstream. Both proteins were shown to interact with a large variety of transported substrates, and earlier studies suggested that MRPs may work as co-transporters for different molecules. In the present study we expressed the human MRP2 and MRP3 proteins in insect cells and examined their transport and ATPase characteristics in isolated, inside-out membrane vesicles. We found that the primary active transport of estradiol-17-beta-d-glucuronide (E217betaG), a major product of human steroid metabolism, was differently modulated by bile acids and organic anions in the case of human MRP2 and MRP3. Active E217betaG transport by MRP2 was significantly stimulated by the organic anions indomethacin, furosemide, and probenecid and by several conjugated bile acids. In contrast, all of these agents inhibited E217betaG transport by MRP3. We found that in the case of MRP2, ATP-dependent vesicular bile acid transport was increased by E217betaG, and the results indicated an allosteric cross-stimulation, probably a co-transport of bile acids and glucuronate conjugates through this protein. There was no such stimulation of bile acid transport by MRP3. In conclusion, the different transport modulation of MRPs by bile acids and anionic drugs could play a major role in regulating physiological and pathological metabolite fluxes in the human liver.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bile Acids and Salts, http://linkedlifedata.com/resource/pubmed/chemical/Carboxylic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Estradiol, http://linkedlifedata.com/resource/pubmed/chemical/Glucuronides, http://linkedlifedata.com/resource/pubmed/chemical/MRP2 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated..., http://linkedlifedata.com/resource/pubmed/chemical/Radioactive Tracers, http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins, http://linkedlifedata.com/resource/pubmed/chemical/estradiol-17 beta-glucuronide, http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23529-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions.
pubmed:affiliation
National Medical Center, Institute of Haematology and Immunology, Membrane Research Group of the Hungarian Academy of Sciences.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't