scholarly journals Canalicular Bile Flow and Bromosulfophthalein Transport Maximum: The Effect of a Bile Salt-Independent Choleretic, Sc-2644

1974 ◽  
Vol 66 (5) ◽  
pp. 1046-1053 ◽  
Author(s):  
G.E. Gibson ◽  
E.L. Forker
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Canalicular Bile

Canalicular bile salt-independent bile formation: concepts and clues from electrolyte transport in rat liver

1983 ◽  
Vol 244 (3) ◽  
pp. G233-G246 ◽  
Author(s):  
J. Graf
Keyword(s):  
Bile Salt ◽  
Water Flow ◽  
Rat Liver ◽  
Bile Flow ◽  
Electrolyte Transport ◽  
Osmotic Gradient ◽  
Solvent Drag ◽  
Concentration Gradients ◽  
Inorganic Ion ◽  
Canalicular Bile

Studies on canalicular electrolyte transport are reviewed with reference to the concept that hepatocellular inorganic ion secretion may provide an osmotic drive for canalicular water flow. Cellular transport of electrolytes and of some nonelectrolytes appears directly or indirectly (cotransport or potential-sensitive transport) related to the activity of Na+-K+-ATPase of the sinusoidal cell membrane, but the role of the enzyme in regulating bile flow remains undetermined. Bile secretion of the isolated rat liver continues in the absence of either Na+, K+, Cl-, or HCO-3 when these ions are replaced in the perfusion medium by other permanent ions. Transepithelial salt concentration gradients, established experimentally, cause transient changes of bile flow and dissipate very quickly. Isotopic ion equilibration between sinusoids and bile proceeds faster than between sinusoids and liver cells. Both observations indicate extensive electrolyte diffusion through a paracellular shunt pathway. This pathway appears preferentially permeable to cations, and it restricts permeation of molecules of the size of sucrose (no apparent diffusion or effects of solvent drag) or bile acids (no backleak). In promoting canalicular osmotic water flow, transepithelial concentration gradients of NaCl are less effective than those of sucrose, revealing a reflection coefficient of NaCl of 0.3. By perfusion with hypertonic medium containing sucrose, bile flow is reduced. Bile production against this opposing osmotic gradient is accomplished by an increase in biliary organic anion concentration. Inorganic ion concentrations essentially conform to a Gibbs-Donnan distribution across the canalicular epithelium, established by the presence of impermeant anions in bile. Hence, the luminal electrical potential is expected to be negative with respect to the sinusoids. It is concluded that biliary secretion of endogenous organic anions is the major osmotic driving force for canalicular bile salt-independent bile flow and that transport of inorganic ions into bile results mainly from diffusion and solvent drag.

Importance of bicarbonate in bile salt independent fraction of bile flow.

1978 ◽  
Vol 235 (2) ◽  
pp. E158 ◽  
Author(s):  
W G Hardison ◽  
C A Wood
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Transport Mechanism ◽  
Excretion Rate ◽  
Organic Anion ◽  
Weak Acid ◽  
Anion Transport ◽  
Bicarbonate Transport ◽  
Canalicular Membrane ◽  
Bile Canalicular Membrane

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane.

Biliary excretion of dye in dogs infused with BSP or its glutathione conjugate

1976 ◽  
Vol 231 (2) ◽  
pp. 399-407 ◽  
Author(s):  
JL Barnhart ◽  
B Combes
Keyword(s):  
Biliary Excretion ◽  
Bile Flow ◽  
Additional Mechanism ◽  
Glutathione Conjugate ◽  
Canalicular Bile ◽  
Transport Carrier ◽  
Per Se ◽  
Osmotic Activity ◽  
Conjugated Metabolites

A comparison of the maximal rates of biliary excretion (Tm), of dye in dogs infused with either BSP or its glutathione conjugate (BSP-GSH) was carried out. Tm was much higher when BSP-GSH rather than BSP was infused. This was accounted for by a significantly higher concentration of dye in bile of dogs receiving BSP-GSH. Evidence is presented that BSP and its conjugated metabolites compete for a common transport carrier and that BSP disproportionately depresses the biliary excretion of conjugated dye compounds. This latter observation accounts for the depressed dye Tm found during infusion of BSP. Choleresis invariably accompanied dye excretion. When BSP-GSH was infused, enhanced bile flow could be accounted for by the predicted osmotic activity of dye transported into bile. By contrast, the choleresis measured during infusion of BSP was significantly greater than that predicted. An additional mechanism for choleresis is operative, therefore, when unconjugated BSP is infused. Administration of taurocholate enhanced dye Tm when BSP-GSH was infused. Since increments of canalicular bile flow induced by theophylline and glucagon did not enhance dye excretion into bile, this effect by taurocholate appears to be related to taurocholate excretion per se rather than to the enhanced canalicular bile flow which accompanies its 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.

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