Pathophysiology of the enterohepatic circulation of bile acids

Matern, Siegfried; Gerok, W.

doi:10.1007/bfb0036117

Cited by 54 publications

(19 citation statements)

References 317 publications

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“…Furthermore, conjugation of bile acids with amino acids appears to decrease the affinity of bile acids to UDP-glucuronosyltransferase, since in the presence of glycolithocholic acid a sixfold lower affinity to hepatic microsomal UDP-glucuronosyltransferase was observed, compared with unconjugated lithocholic acid (Table II). Since, according to the present study in man, unconjugated bile acids appear to be substrates of higher affinity to hepatic and extrahepatic bile acid UDP-glucuronosyltransferase(s) (Table II) Unconjugated primary, secondary, and tertiary bile acids were recently found in serum samples of healthy subjects (7,42), and were shown to increase to concentrations between two and three micromole per liter after breakfast (43). The existence of unconjugated bile acids in serum of healthy subjects and the recent finding of more than 20 individual bile acid glucuronides in urine of healthy subjects, most of which were otherwise unconjugated (4), indicate that glucuronidation of unconjugated bile acids plays a physiological role in bile acid metabolism in health.…”

Section: Discussionmentioning

confidence: 52%

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Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Matern¹,

Matern²,

Farthmann³

et al. 1984

J. Clin. Invest.

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Abstract. Microsomal UDP-glucuronosyltransferase activity toward the bile acids (chenodeoxycholic, deoxycholic, ursodeoxycholic, lithocholic, and glycolithocholic) has been detected in human specimens of liver, kidney, and intestinal mucosa. The characteristics of hepatic and extrahepatic UDP-glucuronosyltransferase activities toward these bile acids were compared with respect to kinetic parameters and other catalytic properties. Whereas no organspecific differences in the affinities of individual bile acids to hepatic and extrahepatic UDP-glucuronosyltransferases were observed, the individual bile acids showed reaction rates in liver that were about twice the rates estimated in kidney and about twice to three times the rates observed in duodenal mucosa. In intestinal mucosa the rate of chenodeoxycholic acid glucuronidation exhibited a progressive decrease from duodenum to colon, where it was 30%o of the duodenal level.

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Section: Discussionmentioning

confidence: 52%

“…Therefore, in addition to sulphate esterification (5), conjugation of bile acids with glucuronic acid may serve as a protective mechanism against accumulation of potentially toxic bile acids (6)(7)(8)(9). However, little is known about the UDP-glucuronosyltransferase(s) involved in the glucuronidation of bile acids in man.…”

Section: Introductionmentioning

confidence: 99%

Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Matern¹,

Matern²,

Farthmann³

et al. 1984

J. Clin. Invest.

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“…Since monohydroxy bile acids may be present at micromolar concentrations in portal-vein plasma under pathological conditions (Matern & Gerok, 1979), the question arises whether the ER of other cell types is the target of the Ca2+-permeabilizing action of these molecules. To assess this point, Ca2+ responses to taurolithocholate in rat hepatocytes were compared with those displayed by human platelets (Rink & Sage, 1990) and the neuroblastoma NG108-15 cell line (Hamprecht, 1977;Nirenberg et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Effects of taurolithocholate, a Ca2+-mobilizing agent, on cell Ca2+ in rat hepatocytes, human platelets and neuroblastoma NG108-15 cell line

Coquil

Berthon

Chomiki

et al. 1991

Biochemical Journal

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The monohydroxy bile acid taurolithocholate permeabilizes the endoplasmic reticulum to Ca2+ in rat liver cells. To assess whether this action on the endoplasmic reticulum was restricted to this tissue, the effects of bile acid were investigated in two cell types quite unrelated to rat hepatocyte, namely human platelets and the neuronal NG108-15 cell line. The results showed that taurolithocholate (3-100,UM) had no effect on free cytosolic [Ca2+] in human platelets and NG108-15 cells, whereas it increased it from 180 to 520 nm in rat hepatocytes. INTRODUCTIONCertain bile acids such as the monohydroxy bile acid taurolithocholate (EC50 = 20 UM) markedly alter cell Ca2+ metabolism in isolated rat hepatocytes. In suspensions of intact cells,

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“…In the liver, bile salts are rapidly cleared from the portal blood by a well characterized sodium-dependent carrier-mediated process (1)(2)(3). In contrast, cellular translocation and biliary seretion are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Bile Salt Transport in Rat Liver

Simon¹,

Sutherland²,

Gonzalez³

1982

J. Clin. Invest.

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A B S T R A C T Expansion of the bile salt pool size in rats increases maximum excretory capacity for taurocholate. We examined whether increased bile salt transport is due to recruitment of centrolobular transport units or rather to adaptive changes in the hepatocyte. Daily sodium cholate (100 mg/100 g body wt) was administered orally to rats. This treatment was well tolerated for at least 4 d and produced an 8.2-fold expansion of the bile salt pool. This expanded pool consisted predominently (99%) of cholic and deoxycholic acids. Significantly increased bile salt transport was not observed until 16 h after bile acid loading, and maximum elevations of transport capacity to 2.3-fold of control required -2 d. In contrast, maximum sulfobromophthalein excretion rates increased 2.2-fold as early as 4 h and actually fell to 1.5-fold increase at 4 d. We studied the possibility that this adaptive increase in bile salt secretory transport was due to changes in canalicular surface membrane area, lipid composition, or increased number of putative carriers. Canalicular membrane protein recovery and the specific activities of leucine aminopeptidase, Mg++-ATPase and 5'-nucleotidase activities were unaltered by bile salt pool expansion. The content of free and esterified cholesterol and total phospholipids was unchanged in liver surface membrane fractions compared with control values. In contrast, sodium cholate administration seThis work was presented, in part,

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Pathophysiology of the enterohepatic circulation of bile acids

Cited by 54 publications

References 317 publications

Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Effects of taurolithocholate, a Ca2+-mobilizing agent, on cell Ca2+ in rat hepatocytes, human platelets and neuroblastoma NG108-15 cell line

Regulation of Bile Salt Transport in Rat Liver

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