scholarly journals Enzymes and proteins in bile Variations in output in rat cannula bile during and after depletion of the bile-salt pool

1981 ◽  
Vol 196 (1) ◽  
pp. 11-16 ◽  
Author(s):  
P P Godfrey ◽  
M J Warner ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Bile Salt ◽  
Bile Salts ◽  
Lysosomal Enzymes ◽  
Protein Concentration ◽  
Enterohepatic Circulation ◽  
Cell Damage ◽  
Membrane Enzymes ◽  
Rat Bile

The protein concentration in bile from several species is reported. The changes in output of protein, bile salts and several enzymes have been followed in rat bile over a 48 h cannulation period. Bile-salt concentration dropped rapidly owing to interruption of the enterohepatic circulation but the output of protein, lysosomal enzymes [acid phosphatase (EC 3.1.3.2) and beta-D-glucuronidase (EC 3.2.1.31)] and plasma-membrane enzymes [5′-nucleotidase (EC 3.1.3.5) and phosphodiesterase I (EC 3.1.4.1)] was maintained. Liver cell damage, monitored by output of lactate dehydrogenase, was very low throughout. Protein, lysosomal enzymes and plasma-membrane enzymes showed different patterns of output with time, but all showed a net increase between 12 and 24 h. The output of lysosomal and plasma-membrane enzymes was between 1 and 5% of the total liver complement over the first 24 h; if inhibition by biliary components is taken into account the output of some of these enzymes, particularly acid phosphatase, may be greater. Ultracentrifugation of bile showed that as the concentration of bile salts decreases the proportion of plasma-membrane enzymes in a sedimentable form increases. The results are discussed in relation to other studies of biliary proteins and to studies of the perturbation of membranes and cells with bile salts.

scholarly journals Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers

1983 ◽  
Vol 216 (1) ◽  
pp. 107-111 ◽  
Author(s):  
S G Barnwell ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Bile Flow ◽  
Bile Salts ◽  
Cell Damage ◽  
Characteristic Difference ◽  
Membrane Enzymes ◽  
Hepatobiliary System ◽  
Rat Livers

Isolated perfused rat livers were used to study the effects of taurochenodeoxycholate (TCDC) and tauroursodeoxycholate (TUDC) upon some aspects of biliary composition. After depletion of the endogenous bile salt pool of the liver, introduction of either bile salt brought about increases in bile flow, bile salt output and biliary phospholipid output. Taurochenodeoxycholate needed a lower biliary concentration to produce phospholipid output than did tauroursodeoxycholate. TCDC perfusion caused a substantial output of plasma-membrane enzymes (5′-nucleotidase and alkaline phosphodiesterase) into the bile, whereas TUDC caused little output of either enzyme; this may represent a characteristic difference between the effects of the two bile salts on the hepatobiliary system. The results from TUDC perfusion indicate also that much of the output of biliary phospholipid promoted by bile salts, may be independent of the output of plasma-membrane enzymes promoted by bile salts.

scholarly journals The effects of colchicine on secretion into bile of bile salts, phospholipids, cholesterol and plasma membrane enzymes: bile salts are secreted unaccompanied by phospholipids and cholesterol

1984 ◽  
Vol 220 (3) ◽  
pp. 723-731 ◽  
Author(s):  
S G Barnwell ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Protective Effect ◽  
Bile Salt ◽  
Aspartate Aminotransferase ◽  
Bile Salts ◽  
Membrane Damage ◽  
Aminotransferase Activity ◽  
Canalicular Membrane ◽  
Membrane Enzymes ◽  
Taurocholate Transport

Colchicine, a drug which interferes with microtubular function, has no effect on the secretion of taurodehydrocholate into bile; it is therefore suggested that bile salts are unlikely to be packaged in vesicles during cellular transit from sinusoidal to canalicular membranes. Colchicine greatly reduces the secretion of phospholipid and cholesterol into bile; it is suggested that this is due to an interruption in the supply of vesicles bringing lipids to repair the canalicular membrane during bile salt output. In the absence of the protective effect of a continuous supply of repair vesicles, micelleforming bile salts damage the canalicular membrane; the increased concentration of plasma membrane enzymes in bile and the increased aspartate aminotransferase activity in plasma and bile are evidence of this damage. Damage to the canalicular membrane may also be an explanation for the reduction in taurocholate transport and the taurocholate-induced cholestasis which are seen with colchicine-treated livers. Such membrane damage is not observed in colchicine-treated livers during the secretion of the non-micelle forming bile salt, taurodehydrocholate.

scholarly journals Biliary protein output by isolated perfused rat livers. Effects of bile salts

1983 ◽  
Vol 210 (2) ◽  
pp. 549-557 ◽  
Author(s):  
S G Barnwell ◽  
P P Godfrey ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Bile Salts ◽  
Serum Proteins ◽  
Critical Micellar Concentration ◽  
Rapid Decline ◽  
Perfusion Medium ◽  
Rat Serum ◽  
Membrane Enzymes ◽  
Rat Livers

The output of proteins into bile was studied by using isolated perfused rat livers. Replacement of rat blood with defined perfusion media deprived the liver of rat serum proteins (albumin, immunoglobulin A) and resulted in a rapid decline in the amounts of these proteins in bile. When bovine serum albumin was incorporated into the perfusion medium it appeared in bile within 20 min and the amount in the bile was determined by the concentration of the protein in the perfusion medium. The use of a defined perfusion medium also deprived the livers of bile salts and the amounts of these, and of plasma-membrane enzymes [5′-nucleotidase (EC 3.1.3.5) and phosphodiesterase I], in bile declined rapidly. Introduction of micelle-forming bile salts (taurocholate or glycodeoxycholate) to the perfusion medium 80 min after liver isolation markedly increased the output of plasma-membrane enzymes but had no effect on the other proteins. The magnitude of this response was dependent on the bile salt used and its concentration in bile; there was little effect on plasma-membrane enzyme output until the critical micellar concentration of the bile salt had been exceeded in the bile. A bile salt analogue, taurodehydrocholate, which does not form micelles, did not produce the enhanced output of plasma-membrane enzymes. This work supports the view that the output of plasma-membrane enzymes in bile is a consequence of bile salt output and also provides evidence for mechanisms by which serum proteins enter the bile.

Bile salt related secretion of acid phosphatase in rat bile

1986 ◽  
Vol 64 (11) ◽  
pp. 1347-1352 ◽  
Author(s):  
Raul A. Marinelli ◽  
Marcelo G. Luquita ◽  
Emilio A. Rodríguez Garay
Keyword(s):  
Acid Phosphatase ◽  
Bile Salt ◽  
Bile Salts ◽  
Sodium Taurocholate ◽  
Experimental Models ◽  
Experimental Conditions ◽  
Bile Fistula ◽  
Salt Depletion ◽  
Protein Output ◽  
Rat Bile

The biliary excretion of bile salts, lysosomal acid phosphatase, and total proteins were studied in rats under different experimental conditions: (i) during bile salt loss through a bile fistula and (ii) after loading with exogenous sodium taurocholate. The experimental models were suitable to demonstrate that variations in the excretion of bile salts were associated with those of acid phosphatase output. During bile salt depletion, acid phosphatase output showed a decrease parallel to that of bile salts. Following a single i.v. injection of sodium taurocholate and during its i.v. infusion, a rapid increase of acid phosphatase excretion in bile was seen. The patterns of enzyme outputs observed after administration of sodium taurocholate suggested a bulk discharge in bile of lysosomal contents. The profiles of protein output were similar to those of acid phosphatase suggesting an association between the secretory mechanism of these bile constituents. In contrast to sodium taurocholate, 4-methylumbelliferone, which also increases canalicular bile flow, did not produce changes in the excretory patterns of the bile components studied. Therefore, the results suggested a bile salt related secretion of acid phosphatase in the rat, which may involve protein secretion in bile.

Effect of intestinal resection on bile salt absorption in dogs

1965 ◽  
Vol 208 (2) ◽  
pp. 363-369 ◽  
Author(s):  
M. R. Playoust ◽  
Leon Lack ◽  
I. M. Weiner
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Sodium Taurocholate ◽  
Intestinal Resection ◽  
High Fat ◽  
Salt Absorption ◽  
Complete Failure ◽  
Fat Meal

The efficiency of intestinal absorption of bile salts was evaluated by studying the rate of disappearance of radioactivity from the bile of dogs after the intravenous administration of sodium taurocholate-24-C14. Bile was sampled through an indwelling tube in the gall bladder. One day after a high-fat meal normal dogs retained 48% of the radioactivity; dogs with resection of the jejunum retained 48%, whereas those with resection of the ileum retained only 3% in the bile. This is consistent with previous observations that the ileum is the site of bile salt absorption in vitro and in anesthetized animals. Animals with resection of the ileum exhibited significant steatorrhea; however, three-fourths of the ingested fat was absorbed in spite of almost complete failure to absorb bile salts. This indicates that fat and bile salts are not normally absorbed together. Elimination of enterohepatic circulation of bile salts by resection of the ileum contributes to the observed steatorrhea.

EFFECTS OF PHENOBARBITAL ON BILE SALT METABOLISM IN CHOLESTASIS DUE TO INTRAHEPATIC BILE DUCT HYPOPLASIA

PEDIATRICS ◽  
1973 ◽  
Vol 51 (6) ◽  
pp. 992-997
Author(s):  
Adolf Stiehl ◽  
M. Thaler ◽  
William H. Admirand
Keyword(s):  
Bile Duct ◽  
Bile Salt ◽  
Peripheral Blood ◽  
Bile Salts ◽  
Bile Ducts ◽  
Enterohepatic Circulation ◽  
Control Period ◽  
Intrahepatic Bile Duct ◽  
Total Serum ◽  
Salt Excretion

The effects of phenobarbital (PB) on bile salt metabolism in a patient with severe cholestasis due to congenital paucity of perilobular bile ducts were studied with 14C-cholate and 3H-chenodeoxycholate. During the control period (without PB) cholate was the predominant bile salt in the peripheral blood, whereas chenodeoxycholate was predominant in the total bile salt pool. This difference in the distribution of the two primary bile salts appeared to be caused by relatively greater impairment of excretion of cholate from the liver cell into the bile. PB administration caused a decrease in the total serum bile salt concentration (from 132 to 62µg/ml), in the total bile salt pool (from 412 to 304 mg) and in the biologic half-life (cholate from 106 to 34 hours; chenodeoxycholate from 77 to 42 hours). The proportion of the total bile salt pool present in the peripheral blood decreased from 16.8% to 11.7%. In addition, PB markedly increased the fecal bile salt excretion. These data suggest the PB improves pruritus in this type of intrahepatic cholestasis by reducing serum bile salt concentrations. This is accomplished by a shift in bile salts from the peripheral blood into the enterohepatic circulation and by enhancing fecal bile salt excretion.

Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice

2009 ◽  
Vol 297 (3) ◽  
pp. G520-G531 ◽  
Author(s):  
S. Lukovac ◽  
E. L. Los ◽  
F. Stellaard ◽  
E. H. H. M. Rings ◽  
H. J. Verkade
Keyword(s):  
Fatty Acid ◽  
Bile Salt ◽  
Mrna Expression ◽  
Essential Fatty Acid ◽  
Bile Flow ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Synthesis Rate ◽  
Bile Production ◽  
Deficient Mice

Essential fatty acid (EFA) deficiency in mice has been associated with increased bile production, which is mainly determined by the enterohepatic circulation (EHC) of bile salts. To establish the mechanism underlying the increased bile production, we characterized in detail the EHC of bile salts in EFA-deficient mice using stable isotope technique, without interrupting the normal EHC. Farnesoid X receptor (FXR) has been proposed as an important regulator of bile salt synthesis and homeostasis. In Fxr −/− mice we additionally investigated to what extent alterations in bile production during EFA deficiency were FXR dependent. Furthermore, we tested in differentiating Caco-2 cells the effects of EFA deficiency on expression of FXR-target genes relevant for feedback regulation of bile salt synthesis. EFA deficiency-enhanced bile flow and biliary bile salt secretion were associated with elevated bile salt pool size and synthesis rate (+146 and +42%, respectively, P < 0.05), despite increased ileal bile salt reabsorption (+228%, P < 0.05). Cyp7a1 mRNA expression was unaffected in EFA-deficient mice. However, ileal mRNA expression of Fgf15 (inhibitor of bile salt synthesis) was significantly reduced, in agreement with absent inhibition of the hepatic bile salt synthesis. Bile flow and biliary secretion were enhanced to the same extent in EFA-deficient wild-type and Fxr −/− mice, indicating contribution of other factors besides FXR in regulation of EHC during EFA deficiency. In vitro experiments show reduced induction of mRNA expression of relevant genes upon chenodeoxycholic acid and a selective FXR agonist GW4064 stimulation in EFA-deficient Caco-2 cells. In conclusion, our data indicate that EFA deficiency is associated with interrupted negative feedback of bile salt synthesis, possibly because of reduced ileal Fgf15 expression.

Bile Flow and Composition During Bile Acid Depletion and Administration

1974 ◽  
Vol 52 (2) ◽  
pp. 334-348 ◽  
Author(s):  
Curtis D. Klaassen
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Excretion ◽  
Bile Formation ◽  
Bile Acid Excretion ◽  
Rat Bile ◽  
Acid Administration

Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, and percentage solids than rat bile, and rabbit bile had the lowest concentration. The biliary excretion of bile acids was altered in each species by: (1) interruption of the enterohepatic circulation; (2) rapid administration of an exogenous load of bile acids; and (3) constant infusion of an exogenous load of bile acids. Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile. When the enterohepatic circulation was interrupted in the dog and rat, the bile acid concentration markedly decreased with only minor changes in bile flow. This not only supports the theory that there is a bile salt independent fraction of bile formation, but also demonstrates that canalicular bile formation can be maintained at relatively normal rates with almost no excretion of bile acids. Marked discrepancy between bile acid excretion and bile flow was observed in the rat after bile acid administration, in that a marked increase in bile acid excretion was observed but little or no increase in flow. When bile flow was plotted against bile acid excretion for the three species, the slope of the line was less during bile acid administration than during depletion, indicating that the bile acids are accompanied by less water during bile acid administration than during depletion. Variation in the bile flow intercept with zero bile acid excretion (thought to represent the bile salt-independent fraction) was relatively large, which is probably due in part to alteration in the production of the bile salt independent fraction when bile acid secretion is altered. It appears that both the choleretic property of bile acids varies during various rates of bile acid excretion and the bile salt-independent fraction is not constant. Therefore, calculation of the bile salt independent fraction as previously performed should be interpreted with extreme caution. Thus, it appears difficult to determine the quantitative importance of bile acid excretion in bile formation.

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