Effect of choleretics on canalicular transport of protoporphyrin in the rat liver

The major route of protoporphyrin elimination is biliary secretion. To clarify the nature of the secretory process, maximal canalicular secretion of protoporphyrin was determined under basal conditions and after treatment with various choleretics. The maximal secretion of protoporphyrin under basal conditions was 0.07 +/- 0.01 micrograms.min-1.100 g body wt-1. Infusion of physiological amounts of sodium taurocholate increased protoporphyrin secretion 13-fold (0.90 +/- 0.02), primarily by increasing the biliary protoporphyrin concentration. Biliary protoporphyrin secretion tended to plateau in spite of a continued rise in both biliary bile acid secretion and concentration. Infusion of sodium dehydrocholate increased protoporphyrin secretion, but to only 35% of that achieved by sodium taurocholate. Ethacrynic acid and phenobarbital increased bile flow over controls but failed to enhance protoporphyrin transport. Thus, canalicular secretion of protoporphyrin was maximally enhanced by micelle-forming bile acids and unaffected by nonbile acid choleretics. The observed limitation of protoporphyrin secretion may be related to achievement of a canalicular transport maximum or to a toxic effect of protoporphyrin on the transport process.

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Differing effects of norcholate and cholate on bile flow and biliary lipid secretion in the rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.246.1.g67 ◽

1984 ◽

Vol 246 (1) ◽

pp. G67-G71

Author(s):

E. R. O'Maille ◽

S. V. Kozmary ◽

A. F. Hofmann ◽

D. Gurantz

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Bile Acids ◽

Bile Flow ◽

Critical Micellar Concentration ◽

Biliary Lipid ◽

Lipid Secretion ◽

Unit Increase ◽

Cholesterol Secretion ◽

Bile Acid Secretion

The effects of norcholate (a C23 bile acid that differs from cholate in having a side chain containing four rather than five carbon atoms) on bile flow and biliary lipid secretion were compared with those of cholate, using the anesthetized rat with a bile fistula. Norcholate and cholate were infused intravenously over the range of 0.6-6.0 mumol X min-1 X kg-1. Both bile acids were quantitatively secreted into bile; norcholate was secreted predominantly in unconjugated form in contrast to cholate, which was secreted predominantly as its taurine or glycine conjugates. The increase in bile flow per unit increase in bile acid secretion induced by norcholate infusion [17 +/- 3.2 (SD) microliters/mumol, n = 8] was much greater than that induced by cholate infusion (8.6 +/- 0.9 microliters/mumol, n = 9) (P less than 0.001). Both bile acids induced phospholipid and cholesterol secretion. For an increase in bile acid secretion (above control values) of 1 mumol X min-1 X kg-1, the increases in phospholipid secretion [0.052 +/- 0.024 (SD) mumol X min-1 X kg-1, n = 9] and cholesterol secretion (0.0071 +/- 0.0033 mumol X min-1 X kg-1, n = 9) induced by norcholate infusion were much less than those induced by cholate infusion (0.197 +/- 0.05 mumol X min-1 X kg-1, n = 9, and 0.024 +/- 0.011 mumol X min-1 X kg-1, n = 9, respectively; P less than 0.001 for both phospholipid and cholesterol). The strikingly different effects of norcholate on bile flow and biliary lipid secretion were attributed mainly to its possessing a considerably higher critical micellar concentration than cholate.

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Decrease of bile flow and bile acid secretion after stimulation of hepatic nerves in the perfused liver

Journal of Hepatology ◽

10.1016/s0168-8278(87)80261-1 ◽

1987 ◽

Vol 5 ◽

pp. S90

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Bile Flow ◽

Perfused Liver ◽

Hepatic Nerves ◽

Bile Acid Secretion ◽

Stimulation Of

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Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat

Clinical Science ◽

10.1042/cs0750593 ◽

1988 ◽

Vol 75 (6) ◽

pp. 593-599

Author(s):

J. J. Garcia-Marin ◽

J. G. Redondo-Torres ◽

F. Perez-Barriocanal ◽

M. M. Berenson

Keyword(s):

Body Weight ◽

Bile Acid ◽

Bile Flow ◽

Sodium Taurocholate ◽

Protoporphyrin Ix ◽

Inhibitory Effect ◽

Bicarbonate Secretion ◽

Bile Formation ◽

Dose Dependent ◽

Bile Acid Secretion

1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats. 2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min−1 100 g−1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, Pco2, Po2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose. 3. Sodium taurocholate was infused (0.5 μmol min−1 100 g−1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution. 4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min−1 100 g−1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX. 5. These results indicate that in the rat, in vivo, protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.

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EFFECT OF INCREASED BILE FLOW AND BILE ACID SECRETION ON THE HEPATIC ELIMINATION OF SODIUM VALPROATE IN THE CAT

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.1984.tb00269.x ◽

1984 ◽

Vol 11 (3) ◽

pp. 309-317

Author(s):

A. W. Marshall ◽

G. W. Mihaly ◽

R. A. Smallwood ◽

R. G. Hanson ◽

F. J. E. Vajda ◽

...

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Sodium Valproate ◽

Bile Flow ◽

Hepatic Elimination ◽

Bile Acid Secretion

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The effect of methimazole on bile flow and bile acid secretion in the rat

Biochemical Pharmacology ◽

10.1016/0006-2952(88)90129-3 ◽

1988 ◽

Vol 37 (4) ◽

pp. 583-589

Author(s):

Jesus Ruiz ◽

Maria E. Mun̄oz ◽

Alejandro Esteller ◽

Javier Gonzalez

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Bile Flow ◽

Bile Acid Secretion

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Bile acid kinetics and bile secretion in the pony

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1975.229.3.592 ◽

1975 ◽

Vol 229 (3) ◽

pp. 592-597 ◽

Cited By ~ 17

Author(s):

MS Anwer ◽

RR Gronwall ◽

LR Engelking ◽

RD Klentz

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Isotope Dilution ◽

Bile Flow ◽

Pool Size ◽

Synthesis Rate ◽

Bile Acid Pool ◽

Acid Pool ◽

Bile Acid Pool Size ◽

Bile Acid Secretion

Bile acid pool size and synthesis rate were determined by both isotope-dilution and washout methods in ponies with chronic external biliary fistulas. Bile acid pool size (10.9 mumol/kg) and synthesis rate (11.2 mumol/day per kg) estimated by the isotope-dilution method did not differ significantly from pool size (9.4 mumol/kg) and synthesis rate (9.5 mumol/day per kg) estimated by washout method. Bile acid-dependent and -independent fractions of bile flow, determined by a method that circumvents any inevitable correlation of flow to bile acid secretion due to common factors in both parameters, did not differ from those values obtained by linear regression of bile flow versus bile acid secretion. The choleretic effect of infused chenodeoxycholic acid was higher than that of both endogenous bile acid and infused taurocholic acid.

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Taurolithochoiic acid and chlorpromazine cholestasis in the rhesus monkey

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y79-169 ◽

1979 ◽

Vol 57 (10) ◽

pp. 1138-1147 ◽

Cited By ~ 10

Author(s):

S. M. Strasberg ◽

R. M. Kay ◽

R. G. Ilson ◽

C. N. Petrunka ◽

J. E. Paloheimo

Keyword(s):

Bile Acid ◽

Acid Secretion ◽

Bile Flow ◽

Recovery Period ◽

Secretion Rate ◽

Bicarbonate Secretion ◽

Bicarbonate Concentration ◽

Bile Acid Concentration ◽

Dose Dependent ◽

Bile Acid Secretion

Taurolithocholic acid (TLC) and chlorpromazine (CPZ) cholestasis were studied in reversible primate models in order to determine the level of injury, changes in canalicular permeability, and the effects of taurocholic acid (TC) on the production of cholestasis. TLC produced dose-dependent cholestasis. Reductions in bile acid secretion rate and concentration, larger decreases in [14C]erythritol clearance than in total bile flow, and increased bicarbonate concentration in bile indicated that the cholestasis was canalicular in origin. TC prevented cholestasis; it also caused an increased secretion of TLC in bile, but the TLC:TC concentration ratio was unchanged, providing evidence that TC is beneficial because it hastens excretion of TLC from the liver cell in micelles. Permeability to [3H]inulin was increased during the recovery period. CPZ caused reductions in bile flow, bile acid secretion rate, and [14C]erythritol clearance, and almost completely eliminated biliary bicarbonate secretion, suggesting a mixed canalicular and ductular form of cholestasis. When TC was given with CPZ, no reductions in bile acid secretion rate or [14C]erythritol clearance were found but bicarbonate secretion was markedly reduced, bicarbonate concentration diminished, and bile acid concentration increased, i.e., TC protected against the canalicular component of CPZ cholestasis and unmasked the ductular component. Permeability to inulin was increased in three of four animals. TLC cholestasis occurs predominately at the canalicular level, whereas CPZ probably affects bile flow at the ductular level as well. TC protects the hepatocyte against the effects of both agents.

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