Document Detail

Mrp2 is involved in benzylpenicillin-induced choleresis.
MedLine Citation:
PMID:  15194559     Owner:  NLM     Status:  MEDLINE    
Benzylpenicillin (PCG; 180 micromol/kg), a classic beta-lactam antibiotic, was intravenously given to Sprague-Dawley (SD) rats and multidrug resistance-associated protein 2 (Mrp2)-deficient Eisai hyperbilirubinemic rats (EHBR). A percentage of the [(3)H]PCG was excreted into the bile of the rats within 60 min (SD rats: 31.7% and EHBR: 4.3%). Remarkably, a transient increase in the bile flow ( approximately 2-fold) and a slight increase in the total biliary bilirubin excretion were observed in SD rats but not in the EHBR after PCG administration. This suggests that the biliary excretion of PCG and its choleretic effect are Mrp2-dependent. Positive correlations were observed between the biliary excretion rate of PCG and bile flow (r(2) = 0.768) and more remarkably between the biliary excretion rate of GSH and bile flow (r(2) = 0.968). No ATP-dependent uptake of [(3)H]PCG was observed in Mrp2-expressing Sf9 membrane vesicles, whereas other forms of Mrp2-substrate transport were stimulated in the presence of PCG. GSH efflux mediated by human MRP2 expressed in Madin-Darby canine kidney II cells was enhanced in the presence of PCG in a concentration-dependent manner. In conclusion, the choleretic effect of PCG is caused by the stimulation of biliary GSH efflux as well as the concentrative biliary excretion of PCG itself, both of which were Mrp2 dependent.
Kousei Ito; Tomokazu Koresawa; Koichi Nakano; Toshiharu Horie
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  287     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-14     Completed Date:  2004-07-23     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G42-9     Citation Subset:  IM    
Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 263-8675, Japan.
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MeSH Terms
Bile / drug effects,  metabolism,  secretion*
Bilirubin / metabolism
Biological Transport
Cell Line
Cholagogues and Choleretics / blood,  pharmacology*
Glutathione / metabolism
Hyperbilirubinemia / genetics,  metabolism
Liver / drug effects*,  secretion*
Membrane Transport Proteins / deficiency,  metabolism*
Multidrug Resistance-Associated Proteins / deficiency,  metabolism*
Osmolar Concentration
Penicillin G / blood,  pharmacokinetics,  pharmacology*
Rats, Mutant Strains
Rats, Sprague-Dawley
Reg. No./Substance:
0/Cholagogues and Choleretics; 0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/multidrug resistance-associated protein 2; 61-33-6/Penicillin G; 635-65-4/Bilirubin; 70-18-8/Glutathione

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