Biliary lipid secretion in the rat. The uncoupling of biliary cholesterol and phospholipid secretion from bile acid secretion by sulfated glycolithocholic acid

Author(s):  
Folkert Kuipers ◽  
Johannes P.T. Derksen ◽  
Albert Gerding ◽  
Gerrit L. Scherphof ◽  
Roel J. Vonk
1985 ◽  
Vol 69 (1) ◽  
pp. 71-79 ◽  
Author(s):  
A. Reuben ◽  
P. N. Maton ◽  
G. M. Murphy ◽  
R. H. Dowling

1. Biliary lipid secretion rates were measured in non-obese and obese individuals with and without cholesterol gallstones, using a steady-state, amino acid duodenal perfusion method. In addition, biliary lipid secretion rates were measured in five obese gallstone patients receiving high-dose chenodeoxycholic acid therapy (16-22 mg day−1 kg−1). 2. Bile acid secretion rates in the non-obese patients with cholesterol gallstones (563+sem 70 μmol/h, n = 6) were significantly lower than in the non-obese controls (1078 + 210 μmol/h, n = 10, P < 0.05), whereas cholesterol secretion rates were similar in the non-obese individuals with and without gallstones (51+7 and 42+4 μmol/h respectively). 3. In the obese, both with and without gallstones, the major abnormality was hypersecretion of cholesterol (107+7 μmol/h, n = 7, and 81 + 15 μmol/h, n = 7, respectively). Both these values were significantly greater than those in the non-obese controls (P < 0.01-0.02). 4. Biliary cholesterol secretion rates correlated significantly with bile acid secretion rates but, for every mole of bile acid secreted, the obese secreted more cholesterol than the non-obese. 5. Chenodeoxycholic acid treatment lowered biliary cholesterol saturation in obese gallstone patients by reducing biliary cholesterol secretion. 6. These results suggest that there are two major types of defect in biliary lipid secretion in gallstone patients: reduced biliary bile acid secretion in non-obese gallstone patients and excessive biliary cholesterol secretion in the obese.


1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.


1975 ◽  
Vol 229 (3) ◽  
pp. 714-720 ◽  
Author(s):  
NE Hoffman ◽  
DE Donald ◽  
AF Hosmann

An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.


1989 ◽  
Vol 263 (2) ◽  
pp. 513-518 ◽  
Author(s):  
M J Monte ◽  
F Cava ◽  
A Esteller ◽  
R Jimenez

The effects of sodium cyclobutyrate, a synthetic hydrocholeretic drug, on biliary lipid secretion and on the biliary outputs of several plasma-membrane enzymes were investigated in anaesthetized rats. Administration of a single oral dose of cyclobutyrol (0.72 mmol/kg body wt.) reduced biliary concentration and output of cholesterol and phospholipid. However, bile acid secretion was not significantly modified. This uncoupling effect of lipid secretion remained even when the choleretic response to the drug had ceased. It additionally led to a statistically significant decrease in the cholesterol/bile acid and phospholipid/bile acid molar ratios and in the lithogenic index of the bile. The biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were markedly reduced by the drug. When cyclobutyrol was administered to rats which had been previously fed with a high-cholesterol diet, the effects of cyclobutyrol persisted, but were less marked. Our results demonstrate that the bile acid-independent choleresis induced by cyclobutyrol (related to its pharmacokinetic effect) is accompanied by a pharmacodynamic action that selectively reduces the secretion of biliary lipids. This is due to an uncoupling of the secretion of cholesterol and phospholipids from that of bile acids. Possible explanations for the biliary response to cyclobutyrol are discussed.


1990 ◽  
Vol 99 (5) ◽  
pp. 1485-1492 ◽  
Author(s):  
Henkjan J. Verkade ◽  
Marjan J. Wolbers ◽  
Rick Havinga ◽  
Donald R.A. Uges ◽  
Roel J. Vonk ◽  
...  

Hepatology ◽  
1997 ◽  
Vol 26 (3) ◽  
pp. 527-536 ◽  
Author(s):  
M Y El-Mir ◽  
M J Monte ◽  
A I Morales ◽  
M Arevalo ◽  
M A Serrano ◽  
...  

1980 ◽  
Vol 58 (6) ◽  
pp. 545-548 ◽  
Author(s):  
Marta Dubin ◽  
S. Erlinger

1. The effect of phalloidin on bile acid, phospholipid and cholesterol secretion into bile was studied in rats with bile fistulae. 2. Phalloidin, when given for 7 days, induced a significant decrease in biliary cholesterol concentration and cholesterol saturation index. Bile acid and phospholipid concentration in bile remained unchanged. This effect was less marked in animals receiving the drug for 3 days, and not detectable in animals treated for 1 day. 3. These results provide circumstantial evidence for the hypothesis that microfilament dysfunction may lead to alterations in cholesterol secretion into bile.


Hepatology ◽  
1996 ◽  
Vol 24 (5) ◽  
pp. 1224-1229 ◽  
Author(s):  
K Mizuno ◽  
M Hoshino ◽  
T Hayakawa ◽  
H Yamada ◽  
T Nakazawa ◽  
...  

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