Cholestasis induced by sodium taurolithocholate in isolated hamster liver

King, J. E.; Schoenfield, Leslie J.

doi:10.1172/jci106728

Cited by 66 publications

(14 citation statements)

References 27 publications

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“…These studies suggest that bile salt-independent secretion represents a significant portion of canalicular flow in man, as has been previously demonstrated for a variety of species, including the rat (8,9,(23)(24)(25), rabbit (7), hamster (26), and dog (6,27). The estimates of bile salt-independent canalicular flow during control periods averaged 0.155 ml/min or 37% of the average basal flow rate ( (8).…”

Section: Discussionsupporting

confidence: 77%

Canalicular Bile Secretion in Man STUDIES UTILIZING THE BILIARY CLEARANCE OF [14C]MANNITOL

Boyer¹,

Bloomer²

1974

J. Clin. Invest.

128

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Section: Discussionsupporting

confidence: 77%

Canalicular Bile Secretion in Man STUDIES UTILIZING THE BILIARY CLEARANCE OF [14C]MANNITOL

Boyer¹,

Bloomer²

1974

J. Clin. Invest.

128

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“…This bile salt causes cholestasis in the whole animal (21) and in isolated perfused liver (22). Changes of ultrastructure (23,24) and ofactivities of membrane-bound enzymes (25) …”

Section: Resultsmentioning

confidence: 99%

Transcellular transport of fluorescein in hepatocyte monolayers: evidence for functional polarity of cells in culture.

Barth¹,

Schwarz²

1982

Proc. Natl. Acad. Sci. U.S.A.

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The rat liver in vivo transfers bile salts, proteins, and dyes from blood into bile. It is the purpose of this communication to demonstrate the maintenance of this transcellular transport in cultured adult rat hepatocytes. Two minutes after adding fluorescein (20 ,ug/ml) to the culture medium, maximal cellular fluorescence was observed through the fluorescence microscope. Subsequently, intercellular clefts showed a steadily increasing fluorescence with a maximum between 5 and 20 min, resulting in a brightly fluorescent network of intercellular gaps. The following observations are taken as evidence that these findings reflect cellular uptake and canalicular secretion of the dye. First, the same sequence of observations was made upon addition of fluorescein diacetate (a nonfluorescent precursor offluorescein), proving that the compound had been taken up and metabolized in the cells to fluorescein before secretion into intercellular clefts. Second, preincubation of the monolayers with the cholestatic bile salt taurolithocholate (100 j.mol/liter) suppressed almost completely intercellular but not cellular fluorescence. It is concluded that hepatocytes in culture show a functional polarity permitting the transcellular transport of substances bound for biliary secretion.The hepatocyte is an epithelial cell whose morphology and physiology show a marked polarity. Its cell membrane has two distinct domains: the sinusoidal membrane, which mediates solute exchange with blood, and the canalicular membrane, which faces the bile canaliculus and is involved in bile formation (1, 2). Functional polarity is most clearly demonstrated by transcellular transport of bile salts, proteins, and various organic compounds from the blood compartment to bile. This transcellular transfer is mediated by two transport systems-one sinusoidal and one canalicular-operating in sequence (3). Isolated hepatocytes obtained by dissociation ofthe liver after perfusion with collagenase (4) have been described as reaggregating to organotypic structures in monolayer culture (5-8). These cells in culture maintain the capability to take up bile salts by the sinusoidal transport system (9). Moreover, their ultrastructure displays numerous elements that show the anatomical features of bile canaliculi (8,10,11). At present, it is open to debate whether these ultrastructural elements of the cultured hepatocyte are still operative and perform secretory work.Recent reports offunctional polarization of epithelial cells in culture by demonstration ofasymmetric virus budding (12) and transcellular net movement of ions (13,14) in MDCK cells led us to study whether this applies to biliary transport in cultured adult rat hepatocytes. For this purpose, we have investigated uptake and secretion offluorescent dyes that are subject to biliary elimination in vivo (15) with fluorescence microscopy.MATERIALS AND METHODS Materials. Fluorescein was obtained from Drobena GmbH, (Berlin), fluorescein diacetate was from Sigma, taurolithocholate was from Calbiochem, and c...

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“…Our failure to demonstrate increased amounts of THCA in specimens obtained from 11 other patients with neonatal forms of intra-and extrahepatic bile duct anomalies indicates that cholestasis itself is not responsible for the metabolic defect in the metabolism of THCA. Certain bile acids, e.g., the monohydroxy bile acid, 3a-hydroxy-5P-cholan-24-oic acid (lithocholic acid) has been shown to produce cholestasis (33,34) and cirrhosis (35) in experimental animals. The toxicity of THCA has not been thoroughly investigated, although Lee and Whitehouse (36) demonstrated that THCA is a potent uncoupler of oxidative phosphorylation.…”

Section: Identification Of Thca Inmentioning

confidence: 99%

The metabolism of 3alpha, 7alpha, 12alpha-trihydorxy-5beta-cholestan-26-oic acid in two siblings with cholestasis due to intrahepatic bile duct anomalies. An apparent inborn error of cholic acid synthesis.

Hanson¹,

Isenberg²,

Williams³

et al. 1975

J. Clin. Invest.

117

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A B S T R A C T Studies were carried out in a family in which two children with cholestasis due to intrahepatic bile duct anomalies were shown to have increased amounts of the cholic acid precursor, 3a,7a, 12a-trihydroxy-5P-cholestan-26-oic acid (THCA). The metabolism of THCA was studied in one of these patients after an intravenous injection of [8H]THCA, and the cause of the increased amounts of THCA in this condition was found to be due to a metabolic defect in the conversion of this compound into cholic acid. A small amount of ['H]cholic acid was also identified after [3H]THCA administration, confirming that this metabolic defect was incomplete. Varanic acid (3a,7a,12a, 24t-tetrahydroxy-5fi-cholestan-26-oic acid), a metabolite of THCA, could not be identified in either of these patients. By assuming that this compound would be conjugated and excreted if the metabolic block occurred after the formation of varanic acid, the defect in these patients appears to be due to a deficiency of a 24-hydroxylating enzyme system required to convert THCA into varanic acid.This condition appears to be transmitted in an autosomal recessive fashion, because the two affected patients were of opposite sex, and neither a normal Presented in abstract form at the annual meeting of the American

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Cholestasis induced by sodium taurolithocholate in isolated hamster liver

Cited by 66 publications

References 27 publications

Canalicular Bile Secretion in Man STUDIES UTILIZING THE BILIARY CLEARANCE OF [14C]MANNITOL

Canalicular Bile Secretion in Man STUDIES UTILIZING THE BILIARY CLEARANCE OF [14C]MANNITOL

Transcellular transport of fluorescein in hepatocyte monolayers: evidence for functional polarity of cells in culture.

The metabolism of 3alpha, 7alpha, 12alpha-trihydorxy-5beta-cholestan-26-oic acid in two siblings with cholestasis due to intrahepatic bile duct anomalies. An apparent inborn error of cholic acid synthesis.

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