Document Detail


Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells.
MedLine Citation:
PMID:  7815365     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.
Authors:
Y Tomita; M Takano; M Yasuhara; R Hori; K Inui
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  272     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1995 Jan 
Date Detail:
Created Date:  1995-02-08     Completed Date:  1995-02-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  63-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport, Active
Carrier Proteins / metabolism*
Cephalosporins / metabolism*
Dipeptides / metabolism
Hydrogen-Ion Concentration
Intestinal Absorption*
Intestines / metabolism*
Kinetics
Leucine / analogs & derivatives,  metabolism
Male
Rabbits
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cephalosporins; 0/Dipeptides; 58970-76-6/bestatin; 61-90-5/Leucine

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


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