Document Detail


Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.
MedLine Citation:
PMID:  11123367     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chlorogenic acid derivatives were recently identified as novel, potent, and specific inhibitors of the hepatic glucose 6-phosphate translocase. Inhibition of the glucose 6-phosphate translocase leads to a decrease in hepatic glucose production, rendering chlorogenic acid derivatives as potential novel therapeutics in patients with type 2 diabetes. The present study examines the hepatic uptake mechanism of the radiolabeled chlorogenic acid derivative S 1743 into freshly isolated rat hepatocytes. Initial uptake rates were Na(+)-independent and followed saturation kinetics with no superimposition of facilitated diffusion. Inhibition studies demonstrated that other chlorogenic acid derivatives inhibited uptake of the radiolabeled compound S 1743 into rat hepatocytes in the range of 1.1 to 11 microM, whereas the natural chlorogenic acid (up to 100 microM) had no effect at all. In addition, inhibition of S 1743 uptake into rat hepatocytes was found in the presence of sulfobromophthalein, sulfolithocholyltaurine, estrone-3-sulfate, cholyltaurine, verapamil, bumetanide, probenecide, phenol red, digoxin, and ouabain (in decreasing order) but not with N-methylnicotinamide, alpha-ketoglutarate, p-aminohippurate, geneticin sulfate, and 5-sulfosalicylate. The observed inhibition pattern suggested that members of the family of the organic anion transporting polypeptides (Oatps) could be involved in hepatic uptake of chlorogenic acid derivatives. Indeed, S 1743 uptake could be demonstrated in Oatp1- and Oatp2-expressing Xenopus laevis oocytes as well as in Oatp1-expressing Chinese hamster ovary cells. A comparison of the inhibition pattern obtained in hepatocytes compared with that obtained in Oatp1-expressing Chinese hamster ovary cells suggests that facilitated uptake by Oatp1 is a major contributor in total hepatic uptake of chlorogenic acid derivatives.
Authors:
D Schwab; A W Herling; H Hemmerle; G Schubert; B Hagenbuch; H J Burger
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  296     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-02-02     Completed Date:  2001-02-02     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:  91-8     Citation Subset:  IM    
Affiliation:
Aventis Pharma Deutschland GmbH, Frankfurt am Main, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anion Transport Proteins
CHO Cells
Carrier Proteins / metabolism*
Chlorogenic Acid / analogs & derivatives*,  metabolism
Cricetinae
Hepatocytes / drug effects,  metabolism*
Kinetics
Liver / metabolism*
Male
Microsomes, Liver / metabolism
Mitochondrial ADP, ATP Translocases / metabolism
Oocytes / metabolism
Rats
Rats, Sprague-Dawley
Sulfonamides / metabolism*
Xenopus laevis
Chemical
Reg. No./Substance:
0/Anion Transport Proteins; 0/Carrier Proteins; 0/S 1743; 0/Sulfonamides; 327-97-9/Chlorogenic Acid; 9068-80-8/Mitochondrial ADP, ATP Translocases

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