Response to 21‐1766: Challenging the dogma of canalicular bile flow

Hepatology ◽  
2021 ◽  
Author(s):  
Nachiket Vartak ◽  
Jan G Hengstler
Keyword(s):  
Bile Flow ◽  
Canalicular Bile

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.

scholarly journals Sodium Taurocholate Modifies the Bile Acid-Independent Fraction of Canalicular Bile Flow in the Rhesus Monkey

1979 ◽  
Vol 64 (1) ◽  
pp. 312-320 ◽  
Author(s):  
Alfred L. Baker ◽  
R. A. B. Wood ◽  
A. R. Moossa ◽  
James L. Boyer
Keyword(s):  
Bile Acid ◽  
Rhesus Monkey ◽  
Bile Flow ◽  
Sodium Taurocholate ◽  
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.

Intracellular chloride activity in intact rat liver: relationship to membrane potential and bile flow

1987 ◽  
Vol 252 (5) ◽  
pp. G699-G706
Author(s):  
J. G. Fitz ◽  
B. F. Scharschmidt
Keyword(s):  
Membrane Potential ◽  
Bile Flow ◽  
Chloride Transport ◽  
Basolateral Membrane ◽  
Bile Formation ◽  
Intracellular Chloride ◽  
Canalicular Bile ◽  
Intracellular Chloride Activity ◽  
Chloride Activity

Active chloride transport has been described in a variety of epithelia, and intracellular chloride activity (aiCl) in these tissues is generally elevated twofold or more above the level predicted for passive diffusion. To determine whether active chloride transport might contribute to canalicular bile formation, we have used conventional and Cl- -selective microelectrodes to measure aiCl of rat hepatocytes in vivo under a variety of conditions. Under basal conditions, the membrane potential difference averaged -33.2 +/- 3.5 mV (means +/- SD) in 29 animals, and the ratio (R) of observed aiCl (24.8 mM) to that expected for passive distribution at this membrane potential (22.6 mM) was 1.10 +/- 0.08, a value slightly but significantly greater than that predicted for passive distribution. Infusion of alanine (45-mumol bolus, 10.8-mumol/min infusion) in 5 animals hyperpolarized the membrane potential to -43.6 +/- 4.0 mV over 10-15 min and resulted in a significant fall in aiCl to 15.1 +/- 4.8 mM but with no change in R. Infusion of theophylline (577 nmol/min), taurocholate (3-mumol bolus, 810-nmol/min infusion), and ursodeoxycholic acid (4-mumol bolus, 2.13-mumol/min infusion) into 5 animals each increased bile flow by 6.1, 34.1, and 96.8%, respectively, compared with saline-infused controls but did not alter membrane potential or chloride distribution. These observations indicate that aiCl is close to the level predicted for passive distribution under basal conditions, after hyperpolarization of the membrane potential by alanine, and after stimulation of bile flow by a variety of choleretics. By analogy with Cl- -secreting epithelia, it appears unlikely that active chloride transport across the basolateral membrane contributes significantly to canalicular bile formation by the hepatocyte.

Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses.

1978 ◽  
Vol 234 (2) ◽  
pp. E146
Author(s):  
J L Barnhart ◽  
B Combes
Keyword(s):  
Bile Flow ◽  
Total Concentration ◽  
Sodium Taurocholate ◽  
Fixed Amount ◽  
Bile Formation ◽  
Canalicular Bile ◽  
Wide Range ◽  
Bile Production ◽  
Mean Concentration ◽  
Erythritol And Mannitol

The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs during cholereses induced by sodium taurocholate and by secretin. Cery increased equally with the increase in bile flow induced by taurocholate, whereas mannitol entry into bile was partially restricted; deltaCery/deltabile flow averaged 0.96; deltaCmann/deltaCery averaged 0.81. Values for erythritol clearance exceeded bile flow by a constant volume over a wide range of bile flows, a result that suggests distal reabsorption of a fixed amount of fluid, independent of canalicular bile production. During secretin-induced choleresis both Cery and Cmann accompanied 30-40% of the increase in bile flow, and the ratio of Cmann/Cery was 1.02. Thus the secretin-responsive region is permeable to both erythritol and mannitol. This affects the extent to which measured erythritol clearance accurately reflects canalicular bile formation; Cery may underestimate or overestimate canalicular bile flow. The electrolyte composition of bile remained relatively constant over a broad range of bile flows although the characteristics of taurocholate- and secretin-induced biles differed from each other. Taurocholate-stimulated bile was virtually isotonic. Secretin-induced bile had a high total concentration of electrolyte (mean concentration 367 meq/liter) rich in chloride and bicarbonate and was hypertonic.

[14C]erythritol clearance and canalicular bile acid-independent flow in the baboon

1982 ◽  
Vol 242 (5) ◽  
pp. G475-G480
Author(s):  
S. M. Strasberg ◽  
R. G. Ilson ◽  
C. N. Petrunka
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Quantitative Assessment ◽  
Sodium Taurocholate ◽  
Hepatic Bile ◽  
Bile Formation ◽  
Canalicular Bile

The use of [14C]erythritol for the quantitative assessment of hepatic bile formation has been studied in baboons using sodium taurocholate to generate canalicular bile flow. It has been found that increments in [14C]erythritol clearance are equal to taurocholate-induced increments in bile flow, but there was no change in [14C]erythritol clearance when bile flow was increased by secretin. No evidence was found to support the view that bile acids affect bile acid-independent bile flow.

scholarly journals Influence of Cholic and Chenodeoxycholic Acid on Canalicular Bile Flow in Man

1976 ◽  
Vol 70 (6) ◽  
pp. 1121-1124 ◽  
Author(s):  
Leif Lindblad ◽  
Tore Scherstén
Keyword(s):  
Chenodeoxycholic Acid ◽  
Bile Flow ◽  
Canalicular Bile
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