Document Detail


Efflux mechanism of taurocholate across the rat intestinal basolateral membrane.
MedLine Citation:
PMID:  16749859     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the contribution of multidrug resistance associated protein 3 (Mrp3/ABCC3) to the transport of bile acids across the rat intestinal basolateral membrane using the everted sacs. The permeability-surface area (PS) products of taurocholate in the everted sacs of rat jejunum, ileum, and colon were determined in the absence or presence of inhibitors for Mrp3. The results were analyzed to determine the PS product for the uptake across the apical membrane (PS1) and that for the efflux across the basolateral membrane (PS3). The mucosal-to-serosal transport of taurocholate in the ileum was the highest. The concentration-dependent inhibitory effects by all inhibitors in the ileum were observed on both PS1 and PS3 for taurocholate. However, even in the presence of 1 mM of each inhibitor, the decrease of PS3 was low. Additionally, PS3 in the colon, where Mrp3 is expressed at a high level, was not inhibited by MK571 and taurolithocholate-3-sulfate. Unlike PS1, PS3 did not exhibit saturation at the concentration examined. These results suggest that Mrp3 makes only a minor contribution to the efflux of bile acids across the basolateral membrane. Ostalpha-Ostbeta heteromeric transporter is certainly one of the good candidates for such a transporter.
Authors:
Shingo Sakamoto; Hiroshi Suzuki; Hiroyuki Kusuhara; Yuichi Sugiyama
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  3     ISSN:  1543-8384     ISO Abbreviation:  Mol. Pharm.     Publication Date:    2006 May-Jun
Date Detail:
Created Date:  2006-06-05     Completed Date:  2006-08-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-81     Citation Subset:  IM    
Affiliation:
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basement Membrane / metabolism*
Biological Transport* / drug effects
Colon / metabolism
Digoxin / metabolism
Ileum / metabolism
Intestines / metabolism*
Jejunum / metabolism
Male
Multidrug Resistance-Associated Proteins / antagonists & inhibitors,  metabolism*
Quinidine / pharmacology
Rats
Rats, Sprague-Dawley
Taurocholic Acid / metabolism*,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Multidrug Resistance-Associated Proteins; 0/multidrug resistance-associated protein 3; 20830-75-5/Digoxin; 56-54-2/Quinidine; 81-24-3/Taurocholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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