scholarly journals Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse

1996 ◽  
Vol 314 (3) ◽  
pp. 781-786 ◽  
Author(s):  
José CHIANALE ◽  
Valeska VOLLRATH ◽  
Ana M. WIELANDT ◽  
Ludwig AMIGO ◽  
Attilio RIGOTTI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Flow ◽  
Control Group ◽  
Biliary Lipid ◽  
Membrane Domain ◽  
Lipid Secretion ◽  
Pharmacological Modulation ◽  
P Glycoprotein ◽  
Liver Gene ◽  
Plasma Membrane Domain

Disruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glycoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates: ciprofibrate, 660±155% (as compared with control group); clofibrate, 611±77%; bezafibrate, 410±47%; fenofibrate, 310±52%; gemfibrozil, 190±25% (P < 0.05 compared with control group). Induction of expression of the mdr gene family was specific to the mdr2 gene. Two- to three-fold increases in P-glycoprotein immunodetection were evident on the canalicular plasma-membrane domain of clofibrate- and ciprofibrate-treated mice. Biliary phospholipid output increased from 4.2±1.2 nmol/min per g of liver in the control group to 8.5±0.6, 7.1±2.9 and 5.8±2.5 in ciprofibrate-, clofibrate- and bezafibrate-treated mice respectively (P < 0.05 compared with control group). Moreover, a significant correlation between biliary phospholipid output and the relative levels of mdr2 mRNA was found (r = 0.86; P < 0.05). In treated animals, bile flow as well as cholesterol and bile acid outputs remained unchanged. Our findings constitute the first evidence that pharmacological modulation of biliary lipid secretion mediated by fibrates can be related to the overexpression of a specific liver gene product, the mdr2 P-glycoprotein, and are consistent with the hypothesis that the mdr2 P-glycoprotein isoform plays a crucial role in the secretion of biliary phospholipid.

Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

1984 ◽  
Vol 246 (1) ◽  
pp. G67-G71
Author(s):  
E. R. O'Maille ◽  
S. V. Kozmary ◽  
A. F. Hofmann ◽  
D. Gurantz
Keyword(s):  
Bile Acid ◽  
Acid Secretion ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Biliary Lipid ◽  
Lipid Secretion ◽  
Unit Increase ◽  
Cholesterol Secretion ◽  
Bile Acid Secretion

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.

Liver gene expression in relation to hepatic steatosis and lipid secretion in two duck species

2010 ◽  
Vol 41 (1) ◽  
pp. 12-20 ◽  
Author(s):  
F. Hérault ◽  
G. Saez ◽  
E. Robert ◽  
A. Al Mohammad ◽  
S. Davail ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatic Steatosis ◽  
Lipid Secretion ◽  
Duck Species ◽  
Liver Gene

Differing effects of hydroxy-7-oxotaurine-conjugated bile acids on bile flow and biliary lipid secretion in dogs

1984 ◽  
Vol 246 (2) ◽  
pp. G166-G172
Author(s):  
R. G. Danzinger ◽  
M. Nakagaki ◽  
A. F. Hofmann ◽  
E. B. Ljungwe
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Critical Micellar Concentration ◽  
Independent Effect ◽  
Biliary Lipid ◽  
Compound I ◽  
Lipid Secretion ◽  
The Individual

The effects on bile flow and biliary lipid secretion of two taurine-conjugated 7-oxo bile acids, 3 alpha-hydroxy-7-oxocholanoyltaurine (I) and 3 alpha,12 alpha-dihydroxy-7-oxocholanoyltaurine (II), were measured in the unanesthetized, chronic bile fistula dog. Each synthetically prepared compound, or cholyltaurine as control, was infused intravenously at a physiological rate of 1 mumol X kg-1 X min-1 for randomized 90-min periods. Bile samples were collected and analyzed for biliary lipids (bile acids, phospholipid, and cholesterol) and bile acid composition. Both compounds were secreted efficiently in bile, recovery averaging 90%. The trisubstituted compound (II) induced a greater choleresis and less phospholipid and cholesterol secretion than the disubstituted compound (I) or cholyltaurine. Each oxo compound was partially reduced during hepatic passage: about 47% of I (to mostly chenodeoxycholyltaurine) and about 30% of II (to mostly cholyltaurine). The effect of the individual bile acids on biliary lipid secretion was then calculated by assuming that a) the infused bile acid induced biliary lipid secretion after its hepatic biotransformation and b) each bile acid or its biotransformation product exerted an independent effect on biliary lipid secretion (expressed as a linkage coefficient, e.g., phospholipid secretion/bile acid secretion). For phospholipid, the calculated linkage coefficient for I was 0.31; for II, 0.07. For cholesterol, the calculated linkage coefficient for I was 0.014; for II, 0.003. In vitro studies indicated that the critical micellar concentration (CMC) in 0.15 M Na+ was 22 mM for I and 40 mM for II (compared with 6 mM for cholyltaurine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of ioglycamide (Biligram) on bile flow and biliary lipid secretion in man.

Gut ◽  
1978 ◽  
Vol 19 (4) ◽  
pp. 300-307 ◽  
Author(s):  
G D Bell ◽  
J Doran ◽  
M Fayadh ◽  
G Murphy ◽  
R H Dowling
Keyword(s):  
Bile Flow ◽  
Biliary Lipid ◽  
Lipid Secretion

scholarly journals Modulation of biliary lipid secretion by forskolin and cyclic AMP analogues

1990 ◽  
Vol 265 (3) ◽  
pp. 879-885 ◽  
Author(s):  
S Hamlin ◽  
K Rahman ◽  
M Carrella ◽  
R Coleman
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Bile Acids ◽  
Bile Flow ◽  
Selective Inhibition ◽  
Biliary Lipid ◽  
Dibutyryl Camp ◽  
Perfusion Medium ◽  
Lipid Secretion ◽  
Rat Livers

Exposure of isolated perfused rat livers to either 100 microM-forskolin, a potent activator of adenylate cyclase, or to 0.5 mM-concentrations of the cAMP analogues chlorophenylthio cAMP (CPTcAMP), dibutyryl cAMP (dbcAMP) and 8-bromo cAMP (8BrcAMP), to provoke increases in intracellular concentrations of cAMP, resulted in marked changes in bile volume and composition. Bile flow reached a peak after 10 min, before declining towards control levels, and an increase in several secretory parameters was also observed at this time. At 20 min, a substantial decrease in the output of both phospholipid and cholesterol was evident, and this suppression of secretion was maintained throughout the remainder of the experiment. The order of effectiveness of the cAMP-elevating agents at decreasing biliary lipid output was CPTcAMP greater than forskolin greater than dbcAMP greater than 8BrcAMP. Biliary output of bile acids was essentially unaltered compared with controls; similarly, no decrease in the secretion of protein and triacylglycerols into the perfusion medium was observed. This suggests that the elevation of intracellular levels of cAMP may cause a selective inhibition of biliary lipid output rather than a more general inhibition of hepatic secretion.

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