Bile Flow and Biliary Excretion Rate of Some Organic Anions in Phenobarbital-Pretreated Rats

Digestion ◽  
1978 ◽  
Vol 17 (3) ◽  
pp. 211-220 ◽  
Author(s):  
E. Fischer ◽  
F. Varga ◽  
Z. Gregus ◽  
A. Gógl
2001 ◽  
Vol 280 (5) ◽  
pp. G858-G865 ◽  
Author(s):  
David W. A. Beno ◽  
Michael R. Uhing ◽  
Masakatsu Goto ◽  
Yong Chen ◽  
Vanida A. Jiyamapa-Serna ◽  
...  

Using a nonstressed chronically catheterized rat model in which the common bile duct was cannulated, we studied endotoxin-induced alterations in hepatic function by measuring changes in the maximal steady-state biliary excretion rate of the anionic dye indocyanine green (ICG). Biliary excretion of ICG was calculated from direct measurements of biliary ICG concentrations and the bile flow rate during a continuous vascular infusion of ICG. Despite significant elevations in mean peak serum tumor necrosis factor-α (TNF-α) concentrations (90.9 ± 16.2 ng/ml), there was no effect on mean rates of bile flow or biliary ICG clearance after administration of 100 μg/kg endotoxin at 6 or 24 h. Significant differences from mean baseline rates of bile flow and biliary ICG excretion did occur after administration of 1,000 μg/kg endotoxin (mean peak TNF-α 129.6 ± 24.4 ng/ml). Furthermore, when rats were treated with up to 16 μg/kg of recombinant TNF-α, there was no change in mean rates of bile flow or ICG biliary clearance compared with baseline values. These data suggest that the complex regulation of biliary excretion is not mediated solely by TNF-α.


2004 ◽  
Vol 287 (1) ◽  
pp. G42-G49 ◽  
Author(s):  
Kousei Ito ◽  
Tomokazu Koresawa ◽  
Koichi Nakano ◽  
Toshiharu Horie

Benzylpenicillin (PCG; 180 μmol/kg), a classic β-lactam antibiotic, was intravenously given to Sprague-Dawley (SD) rats and multidrug resistance-associated protein 2 (Mrp2)-deficient Eisai hyperbilirubinemic rats (EHBR). A percentage of the [3H]PCG was excreted into the bile of the rats within 60 min (SD rats: 31.7% and EHBR: 4.3%). Remarkably, a transient increase in the bile flow (∼2-fold) and a slight increase in the total biliary bilirubin excretion were observed in SD rats but not in the EHBR after PCG administration. This suggests that the biliary excretion of PCG and its choleretic effect are Mrp2-dependent. Positive correlations were observed between the biliary excretion rate of PCG and bile flow ( r2 = 0.768) and more remarkably between the biliary excretion rate of GSH and bile flow ( r2 = 0.968). No ATP-dependent uptake of [3H]PCG was observed in Mrp2-expressing Sf9 membrane vesicles, whereas other forms of Mrp2-substrate transport were stimulated in the presence of PCG. GSH efflux mediated by human MRP2 expressed in Madin-Darby canine kidney II cells was enhanced in the presence of PCG in a concentration-dependent manner. In conclusion, the choleretic effect of PCG is caused by the stimulation of biliary GSH efflux as well as the concentrative biliary excretion of PCG itself, both of which were Mrp2 dependent.


1978 ◽  
Vol 55 (4) ◽  
pp. 399-406 ◽  
Author(s):  
R. J. Vonk ◽  
E. Scholtens ◽  
J. H. Strubbe

1. In unanaesthetized, freely moving rats, which displayed a circadian rhythm in bile flow, hepatic transport of dibromosulphthalein was investigated at midnight when bile flow was high and at noon when bile flow was lower. The influence of pentobarbital anaesthesia and starvation on hepatic transport of dibromosulphthalein was also studied. The influence of bile salts on the hepatic transport process was investigated by interruption of the enterohepatic circulation. 2. Maximal biliary transport of dibromosulphthalein was subject to circadian variations: the biliary transport maximum at night was 25% higher than at noon, although maximal biliary concentration was not significantly altered. The distribution volume was increased by 21% during the night, but the primary hepatic clearance constant was not changed. 3. Pentobarbital anaesthesia decreased the maximal biliary concentration and the maximal biliary excretion rate of dibromosulphthalein, but the primary hepatic clearance constant was not changed. 4. Starvation for 48 h changed the primary hepatic clearance constant as well as the biliary excretion of dibromosulphthalein. 5. Interruption of the enterohepatic circulation of bile did not change the primary hepatic clearance constant of dibromosulphthalein, but decreased biliary excretion of the drug. 6. This study clearly indicates that time of the day, feeding conditions, the use of anaesthetics and interruption of the enterohepatic circulation of bile are important determinants in biliary excretion of cholephilic dyes.


1987 ◽  
Vol 44 (4) ◽  
pp. 846-851 ◽  
Author(s):  
Christopher J. Kemp ◽  
Lawrence R. Curtis

Biliary excretion rate of [14C]taurocholate was 53–63% greater in rainbow trout (Salmo gairdneri) acclimated to and tested at 18 than 14 or 10 °C. Acute 4° temperature shifts up or down increased or decreased respectively biliary excretion rate by 40–53%. Furthermore, 10 °C acclimated fish shifted to 14 °C had 125% greater biliary excretion rate than 18 °C acclimated fish shifted to 14 °C. Apparent hepatic blood flow was greater in fish acclimated to and measured at 18 than 14 or 10 °C but was not different when 10 or 18 °C acclimated fish were measured at 14 °C. Acclimation to 10 versus 18 °C did not affect the Vmax or the temperature/activity relationship for the liver plasma membrane (LPM) Na+,K+-ATPase or the LPM Mg2+ -ATPase but did cause a major shift in the Km of the Na+,K+-ATPase (0.14 and 1.11 mM, respectively). This Km shift was observed at an 18 °C but not a 37 °C assay temperature. Thus, acclimation-induced changes in this enzyme were only observable at physiologically relevant temperature and substrate conditions. Depending on the thermal treatment, both hepatic blood flow and LMP Na+,K+-ATPase may module biliary excretion.


1990 ◽  
Vol 259 (3) ◽  
pp. G453-G461
Author(s):  
M. S. Anwer ◽  
J. M. Atkinson ◽  
P. Zimniak

Bile acid-induced HCO3(-)-rich choleresis may be due to primary activation of sinusoidal Na(+)-H+ exchange or to biliary reabsorption of unconjugated bile acid. To test these hypotheses, we studied the effect of cholate and taurocholate (TC) (infused at 10 mumol/min for 20 min) on net H+ efflux, biliary [HCO3-], and bile flow in perfused rat livers and on intracellular pH (pHi) in isolated hepatocytes. Cholate, but not TC, produced HCO3(-)-rich choleresis. Amiloride and taurine decreased cholate-induced choleresis and HCO3- excretion and biliary excretion of unconjugated cholate. Amiloride, but not taurine, decreased cholate-induced net H+ efflux. Both cholate and TC (200-750 microM) decreased pHi. Cholate was metabolized to a polar compound, most likely cholate glucuronide, in the presence of amiloride. These results are consistent with the hypothesis that the biliary reabsorption of unconjugated cholate may be involved in HCO3(-)-rich choleresis. Amiloride also inhibited net hepatic uptake and biliary excretion of cholate and TC without affecting hepatic content of bile acids. It is suggested that amiloride may decrease the maximal excretion rate of cholate and TC. Since cholate and TC induce amiloride-sensitive net H+ efflux and decrease pHi, it appears that cholate and TC activate Na(+)-H+ exchange indirectly by decreasing pHi.


2000 ◽  
Vol 60 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Joan Riley ◽  
Jerry Styles ◽  
Richard D Verschoyle ◽  
Lesley A Stanley ◽  
Ian N.H White ◽  
...  

1979 ◽  
Vol 237 (6) ◽  
pp. E524
Author(s):  
R J Vonk ◽  
M Danhof ◽  
T Coenraads ◽  
A B van Doorn ◽  
K Keulemans ◽  
...  

The influence of bile salts on hepatic transport of the organic anion dibromosulphthalein (DBSP) was investigated in rats. Bile salts influence the hepatic uptake, intracellular binding, and biliary excretion of DBSP. The overall effect depends on the administered dose of bile salts and DBSP. High doses of bile salts inhibited hepatic uptake of DBSP, whereas low doses of bile salts stimulated bile flow and simultaneously increased maximal biliary excretion of DBSP. The uncharged nonbile salt choleretic ouabain also stimulated biliary DBSP excretion. In contrast, the anionic nonbile salt choleretics, ethacrynic acid and theophylline, did not stimulate biliary excretion of DBSP. Because DBSP inhibited biliary excretion of ethacrynic acid and its metabolites, the lack of a stimulatory effect of ethacrynic acid choleresis might be explained by concomitant inhibition of biliary excretion of DBSP, masking the stimulatory effect of ethacrynic acid. Biliary transport maximum of DBSP was highly correlated with bile flow. The biliary clearance (Vmax/Km) was only moderately changed by bile salt administration, whereas the increase in the maximal biliary excretion rate was more pronounced, implying that the apparent Km for biliary excretion of DBSP was also increased by the bile salts. It is inferred that the stimulation of net biliary excretion of DBSP by bile salts may be due to a diminished transport from bile into the hepatocytes as the consequence of the decreased biliary concentration caused by the choleresis.


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