Linked Life Data

15322236

Source:http://linkedlifedata.com/resource/pubmed/id/15322236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-8-23
pubmed:abstractText
We have proposed previously that the evaluation of transcellular transport across the double-transfected Madin-Darby canine kidney II (MDCK II) monolayer that expresses both human organic anion transporting polypeptide 4 (OATP2/SLC21A6) and multidrug resistance associated protein 2 (MRP2/ABCC2) on the basal and apical membranes, respectively, may be useful in characterizing human biliary excretion (J Biol Chem 277: 6497-6503, 2002). However, to demonstrate that this in vitro system represents in vivo biliary excretion, it is essential to compare in vitro data with in vivo biliary excretion. The problem is that we cannot determine the human biliary excretion for many ligands. In the present study, we have established a double-transfected MDCK II monolayer that expresses both rat Oatp4/Slc21a10 and Mrp2/Abcc2 on the basal and apical membranes, respectively, for the purpose of quantitatively comparing the clearance for transcellular transport with that for in vivo biliary excretion. The basal-to-apical transport of 17beta-estradiol-17beta-d-glucuronide, pravastatin, leukotriene C(4), cyclo-[D-Asp-Pro-d-Val-Leu-d-Trp] (BQ123), temocaprilat, and taurolithocholate 3-sulfate was significantly higher than that in the opposite direction in the double transfectant. Kinetic analysis suggested that that the rate-determining step of these compounds is the uptake process. The extent of the transcellular transport across the rat double-transfectant correlated well with that across the double-transfectant for human OATP2/SLC21A6 and MRP2/ABCC2. Moreover, considering the scaling factor, the clearance values for in vitro transcellular transport correlated well with those for in vivo biliary clearance. The double-transfected MDCK II monolayer may be useful in analyzing the hepatic vectorial transport of organic anions and in predicting in vivo biliary clearance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
450-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Prediction of in vivo biliary clearance from the in vitro transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II monolayer expressing both rat organic anion transporting polypeptide 4 and multidrug resistance associated protein 2.
pubmed:affiliation
Department of Biopharmaceutics, School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't