Document Detail

Small and large unilamellar vesicle membranes as model system for bile acid diffusion in hepatocytes.
MedLine Citation:
PMID:  10415128     Owner:  NLM     Status:  MEDLINE    
Uptake of bile acids into the liver cell occurs via active transport or passive diffusion. In a model system, passive diffusion was studied in liposomes using pyranine fluorescence. Rate constants for the diffusion of diverse more polar or more apolar bile acids were examined. Hydrophobic lithocholic acid (LCA) revealed a maximal rate constant of 0.057 s(-1); with the polar ursodeoxycholic acid (UDCA), the value was 0.019 s(-1). UDCA (3 mol%) effectively decreased the rate constant of 0.1 mM chenodeoxycholic acid (CDCA), whereas cholesterol reached a similar decrease only between 5 and 10 mol%. At higher concentrations of CDCA (above 1 mM) or LCA (0.3-0.4 mM), breaking up of liposomal structure was confirmed by light-scattering decrease and increase of carboxyfluorescein fluorescence. Changes in lipid composition of phosphatidylcholine (PC)- small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs) also caused decreasing rate constants. For a cardiolipin (CL):PC ratio of 1:20 the CDCA (0.1 mM) rate constant was 71% lower (0.015 s(-1)) and for a sphingomyelin (SM):PC ratio of 2:1 the rate constant was 50% lower (0.026 s(-1)). Changes in membrane fluidity were detected using membrane anisotropy measurements with the 1,6-diphenyl-1,3, 5-hexatriene (DPH) method. Membrane fluidity was reduced with cholesterol- but not with CL- or SM-containing SUVs (ratio: cholesterol, CL, SM:PC of 1:5). This model system is currently used for the analysis of more complex lipid vesicles resembling the plasma/hepatocyte membrane, which is either stabilized or destabilized by appropriate conditions. The results should become clinically relevant.
M Hofmann; D Zgouras; P Samaras; C Schumann; K Henzel; G Zimmer; U Leuschner
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  368     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-09-08     Completed Date:  1999-09-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  198-206     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Center of Internal Medicine, Medical Clinic II, Building 11, University Clinics, Theodor-Stern-Kai 7, Frankfurt/Main, 60590, Germany.
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MeSH Terms
Bile Acids and Salts / metabolism*
Cardiolipins / metabolism
Chenodeoxycholic Acid / metabolism
Fluorescence Polarization
Fluorescent Dyes
Lithocholic Acid / metabolism
Liver / cytology,  metabolism*
Models, Biological*
Phosphatidylcholines / metabolism
Sphingomyelins / metabolism
Reg. No./Substance:
0/Arylsulfonates; 0/Bile Acids and Salts; 0/Cardiolipins; 0/Fluorescent Dyes; 0/Liposomes; 0/Phosphatidylcholines; 0/Sphingomyelins; 434-13-9/Lithocholic Acid; 474-25-9/Chenodeoxycholic Acid; 6358-69-6/pyranine

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