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 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.

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 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 Microtubule-independent choleresis and anti-cholestatic action of tauroursodeoxycholate in colchicine-treated rat liver

1992 ◽  
Vol 288 (2) ◽  
pp. 613-617 ◽  
Author(s):  
T Nakai ◽  
K Katagiri ◽  
M Hoshino ◽  
T Hayakawa ◽  
T Ohiwa
Keyword(s):  
Bile Salt ◽  
Ursodeoxycholic Acid ◽  
Bile Flow ◽  
Bile Salts ◽  
Intracellular Transport ◽  
Taurocholic Acid ◽  
Slight Improvement ◽  
Pre Treatment ◽  
Excretion Rates ◽  
Rat Livers

In order to cast light on the anti-cholestatic and cytoprotective properties of ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of bile salts and biliary phospholipids were investigated by using isolated perfused livers from colchicine-pretreated rats. Administration of taurocholic acid (TCA) after colchicine pretreatment induced marked cholestasis. Tauroursodeoxycholic acid (TUDCA) treatment, in contrast, was associated with maintenance of bile flow, with excretion rates of bile acids and phospholipids similar to those in control animals. Furthermore, TCA-induced cholestasis in colchicine-treated rat livers was clearly decreased by co-administration of TUDCA. Although simultaneous addition of UDCA also showed slight improvement, with or without taurine pre-treatment, biliary bile-salt analysis also showed that cholestasis was markedly remitted as the excretion of taurine-conjugated UDCA was increased. The results suggest that the cytoprotective and anti-cholestatic effects of TUDCA may be linked to action at the intrahepatocyte level, represented by mild detergent effects on organelle lipids and preservation of intracellular transport even under microtubule-dysfunctional conditions. In addition, it was indicated that cytoprotective effects of UDCA may also be exerted after its conjugation with taurine inside hepatocytes.

scholarly journals Rapid kinetic analysis of the bile-salt-dependent secretion of phospholipid, cholesterol and a plasma-membrane enzyme into bile

1984 ◽  
Vol 222 (3) ◽  
pp. 631-637 ◽  
Author(s):  
P J Lowe ◽  
S G Barnwell ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Kinetic Analysis ◽  
Bile Salts ◽  
Mixed Micelles ◽  
Biliary Lipid ◽  
Vesicle Traffic ◽  
Membrane Enzyme ◽  
Rat Livers ◽  
Isolated Rat

Isolated rat livers were perfused under ‘one-pass’ conditions and bile was collected at 1 min intervals. After 1 min pulse, taurocholate appeared in the collected bile within 2 min, peak output occurring 2 min later. In contrast, the increased output of phospholipids and cholesterol was slower, peak output occurring 6-11 min after the original pulse of taurocholate. These results suggest that mixed micelles cannot be formed inside the cell or during passage of bile salts through the membrane, since bile salt and lipids should then parallel each other. The bile salts must therefore be pumped into the lumen and the lipids added subsequently, due to the actions of the bile salts in the canalicular lumen. It is suggested that the biliary lipid is obtained from microdomains of biliary-type lipid in the canaliculus membrane, which are vesiculated and solubilized by the action of bile salts. It is also suggested that this biliary-type lipid is brought continuously to the membrane via vesicle traffic; this traffic is increased during increased bile-salt output, and is a process that can be inhibited by colchicine.

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.

scholarly journals Acute effects of cholestatic and choleretic bile salts on vasopressin- and glucagon-induced hepato-biliary calcium fluxes in the perfused rat liver

1992 ◽  
Vol 283 (2) ◽  
pp. 575-581 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Bile Salt ◽  
Rat Liver ◽  
Strong Correlation ◽  
Bile Flow ◽  
Bile Salts ◽  
Perfused Rat Liver ◽  
Acute Effects ◽  
Calcium Fluxes ◽  
Principal Effect

The effects were investigated of the choleretic bile salt glycoursodeoxycholate (G-UDCA) and of the cholestatic bile salt taurochenodeoxycholate (T-CDCA) on changes in perfusate Ca2+, glucose and oxygen and in bile calcium and bile flow induced by the administration of (a) vasopressin, (b) glucagon and (c) glucagon plus vasopressin together to the perfused rat liver [Hamada, Karjalainen, Setchell, Millard & Bygrave (1992) Biochem. J. 281, 387-392]. G-UDCA itself increased the secretion of calcium in the bile several-fold, but its principal effect was to augment each of the above-mentioned metabolic events except glucose and oxygen output; particularly noteworthy was its ability to augment the ‘transients’ in bile calcium and bile flow seen immediately after the administration of vasopressin with or without glucagon. T-CDCA, by contrast, produced opposite effects and attenuated all of the parameters measured, and in particular the transients in bile calcium and bile flow. The data provide evidence of a strong correlation between calcium fluxes occurring on both the sinusoidal and the bile-canalicular membranes and that all are modifiable by glucagon, Ca(2+)-mobilizing hormones and bile salts.

Taurocholate, but not taurodehydrocholate, increases biliary permeability to sucrose

1983 ◽  
Vol 245 (5) ◽  
pp. G651-G655 ◽  
Author(s):  
J. Reichen ◽  
M. Le
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Bile Salts ◽  
Biliary Tree ◽  
Secretory Rate ◽  
Plasma Ratio ◽  
Dose Dependent Fashion ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Salt Secretion

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.

Effect of bile salt on phosphatidylcholine composition and secretion of hepatic high-density lipoproteins

1990 ◽  
Vol 259 (2) ◽  
pp. G205-G211 ◽  
Author(s):  
S. J. Robins ◽  
J. M. Fasulo ◽  
G. M. Patton
Keyword(s):  
Bile Salt ◽  
Molecular Species ◽  
Bile Salts ◽  
Low Density Lipoproteins ◽  
High Density ◽  
High Density Lipoproteins ◽  
Absolute Amount ◽  
Very Low Density Lipoproteins ◽  
Rat Livers ◽  
Isolated Rat

Bile salts are necessary for the secretion of phosphatidylcholines (PCs) in bile and result in the selective secretion of highly hydrophilic molecular species of PC that contain a 16:0 acyl group. To determine the effect of bile salt on the secretion of PCs in lipoproteins, isolated rat livers were perfused with and without taurocholate. The PC composition of very-low-density lipoproteins (VLDL), newly synthesized by the liver, precisely mirrored the composition of PCs in the whole liver and was not changed with the administration of taurocholate. In contrast, both the composition of PCs in high-density lipoproteins (HDL) and the absolute amount of newly synthesized HDL were markedly affected by the administration of taurocholate. With taurocholate the PC content of HDL was increased, HDL was enriched, like bile, in 16:0 molecular species of PC, and the amount of HDL that was recovered in the perfusate was 2.5-fold greater than without taurocholate (P less than 0.001). These findings suggest that VLDL and HDL are differently derived from within the liver, that the PCs of HDL and bile originate from the same hepatic pool or by the same mechanism, and that both the secretion of bile and HDL from the liver are susceptible to regulation by bile salt.

Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into bile

1995 ◽  
Vol 269 (6) ◽  
pp. G801-G812 ◽  
Author(s):  
P. J. Meier
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Bile Salts ◽  
Organic Anion ◽  
Salt Transport ◽  
Salt Flux ◽  
Salt Uptake ◽  
Canalicular Bile ◽  
Salt Secretion ◽  
Bile Salt Transport

An increasingly complex picture has emerged in recent years regarding the bile salt transport polarity of hepatocytes. At the sinusoidal (or basolateral) plasma membrane two bile salt-transporting polypeptides have been cloned. The Na(+)-taurocholate-cotransporting polypeptide (Ntcp) can account for most, if not all, physiological properties of the Na(+)-dependent bile salt uptake function in mammalian hepatocytes. The cloned organic anion-transporting protein (Oatp1) can mediate Na(+)-independent transport of bile salts, sulfobromophthalein, estrogen conjugates, and a variety of other amphipathic cholephilic compounds. Hence, Oatp1 appears to correspond to the previously suggested basolateral multispecific bile sale transporter. Intracellular bile salt transport can be mediated by different pathways. Under basal bile salt flux conditions, conjugated trihydroxy bile salts bind to cytoplasmic binding proteins and reach the canalicular plasma membrane predominantly via cytoplasmic diffusion. More hydrophobic mono- and dihydroxy and high concentrations of trihydroxy bile salts associate with intracellular membrane-bound compartments, including transcytotic vesicles, endoplasmic reticulum (ER), and Golgi complex. A facilitated bile salt diffusion pathway has been demonstrated in the ER. The exact role of these and other (e.g., lysosomes, "tubulovesicular structures") organelles in overall vectorial transport of bile salts across hepatocytes is not yet known. Canalicular bile salt secretion is mediated by two ATP-dependent transport systems, one for monovalent bile salts and the second for divalent sulfated or glucuronidated bile salt conjugates. The latter is identical with the canalicular multispecific organic anion transporter, which also transports other divalent organic anions, such as glutathione S-conjugates. Potential dependent canalicular bile salt secretion has also been suggested to occur, but its exact mechanism and physiological significance remain unclear, since a potential driven bile salt uptake system has also been identified in the ER. Hypothetically, and similar to changes in cell volume, the intracellular potential could also play a role in the regulation of the number of bile salt carriers at the canalicular membrane and thereby indirectly influence the maximal canalicular bile salt transport capacity of hepatocytes.

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