Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. 1991

M Strazzabosco, and S Sakisaka, and T Hayakawa, and J L Boyer
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.

To study how ursodeoxycholic acid (UDCA) increases biliary HCO3- concentration and alkalinizes bile, intracellular pH (pHi) and canalicular pH (pHc) were measured microfluorimetrically in isolated rat hepatocyte couplets (IRHC). Isolated perfused rat livers (IPRL) were also used to assess the roles of Cl-, HCO3-, and zone III hepatocytes. In IRHC, UDCA diminished pHi only when HCO3- was omitted. pHi recovery was inhibited by amiloride. UDCA did not affect pHi recovery from an acid load (NH4Cl) nor modify pHc (+HCO3-). In IPRL, biliary HCO3- concentration increased following UDCA despite removal of Cl- (to inhibit Cl(-)-HCO3- exchanger) or destruction of zone III hepatocytes with digitonin. Moreover, when HCO3- was omitted from the perfusate, biliary pH rose following UDCA even though the hypercholeresis was abolished. Thus 1) hepatic UDCA uptake represents an acid load that is counteracted by Na(+)-H+ exchange when HCO3- is absent; 2) UDCA does not alkalinize pHc; and 3) alkalinization of biliary pH in IPRL is not HCO3- dependent, does not involve Cl(-)-HCO3- exchange, or zonal differences in UDCA metabolism or excretion. UDCA appears to alkalinize bile by protonation within the bile duct lumen. UDCAH may then cross the biliary epithelium.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005452 Fluoresceins A family of spiro(isobenzofuran-1(3H),9'-(9H)xanthen)-3-one derivatives. These are used as dyes, as indicators for various metals, and as fluorescent labels in immunoassays. Tetraiodofluorescein
D005456 Fluorescent Dyes Chemicals that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. Flourescent Agent,Fluorescent Dye,Fluorescent Probe,Fluorescent Probes,Fluorochrome,Fluorochromes,Fluorogenic Substrates,Fluorescence Agents,Fluorescent Agents,Fluorogenic Substrate,Agents, Fluorescence,Agents, Fluorescent,Dyes, Fluorescent,Probes, Fluorescent,Substrates, Fluorogenic

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