A Compartmental Model for Hepatic Transport of Taurocholic Acid in Isolated Perfused Rat Liver

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1978 Jul 17

PMID 683353

Citations 2

Authors

R Kroker

M S Anwer

D HEGNER

Affiliations

Soon will be listed here.

Abstract

In order to characterize the transport of bile acids through the liver and to study the influence of drugs on these processes, a kinetic model for hepatobiliary transport of taurocholic acid (TC) using the isolated perfused liver was developed. After the system was brought to a steady state by infusing TC at a constant rate, a tracer dose of 14C-TC was injected into the medium. The medium disappearance of 14C-TC followed a first-order kinetic with a single rate constant. The plot of the biliary secretion rate of radioactivity versus time revealed a curve composed of at least three exponential components. From the described results and the present knowledge of hepatobiliary transport of bile acids we proposed a three compartment model, composed of a perfusion medium compartment and two liver compartments. Parameters calculated from the model constants agreed well with model-independent estimations. The influence of bromosulfophthalein (BSP) on the kinetic parameters was studied to compare the result with the known effect of BSP on hepatic transport of taurocholic acid. BSP decreased the constant describing the fractional transfer of taurocholic acid from medium into the liver, which is in agreement with the inhibition of hepatic uptake of taurocholic acid by BSP. Thus a three compartment model may adequately define the hepatobiliary transport of taurocholic acid in the isolated perfused rat liver.

Citing Articles

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Proost J, Nijssen H, Strating C, Meijer D, Groothuis G J Pharmacokinet Biopharm. 1993; 21(4):375-94.

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References

Popper H . Liver disease-morphologic considerations. Am J Med. 1954; 16(1):98-117. DOI: 10.1016/0002-9343(54)90326-5. View

Gumucio J, VALDIVIESO V . Studies on the mechanism of the ethynylestradiol impairment of bile flow and bile salt excretion in the rat. Gastroenterology. 1971; 61(3):339-44. View

Mashige F, Imai K, Osuga T . A simple and sensitive assay of total serum bile acids. Clin Chim Acta. 1976; 70(1):79-86. DOI: 10.1016/0009-8981(76)90007-3. View

Schwarz L, Burr R, Schwenk M, Pfaff E, Greim H . Uptake of taurocholic acid into isolated rat-liver cells. Eur J Biochem. 1975; 55(3):617-23. DOI: 10.1111/j.1432-1033.1975.tb02199.x. View

Reichen J, Paumgartner G . Uptake of bile acids by perfused rat liver. Am J Physiol. 1976; 231(3):734-42. DOI: 10.1152/ajplegacy.1976.231.3.734. View

Anwer M, Kroker R, HEGNER D . Cholic acid uptake and isolated rat hepatocytes. Hoppe Seylers Z Physiol Chem. 1976; 357(11):1477-86. DOI: 10.1515/bchm2.1976.357.2.1477. View

Erlinger S, Dhumeaux D . Mechanisms and control of secretion of bile water and electrolytes. Gastroenterology. 1974; 66(2):281-304. View

Kroker R, HEGNER D . Effects of concanavalin A on the isolated perfused rat liver. Naunyn Schmiedebergs Arch Pharmacol. 1975; 289(2):205-15. DOI: 10.1007/BF00501306. View

Kroker R, Anwer M, HEGNER D . The age dependence of bile acid metabolism in rats. Aktuelle Gerontol. 1977; 7(10):539-45. View

10.

Plaa G, Priestly B . Intrahepatic cholestasis induced by drugs and chemicals. Pharmacol Rev. 1976; 28(3):207-73. View

11.

Schwenk M, Schwarz L, Greim H . Taurolithocholate inhibits taurocholate uptake by isolated hepatocytes at low concentrations. Naunyn Schmiedebergs Arch Pharmacol. 1977; 298(2):175-9. DOI: 10.1007/BF00508626. View

12.

HEIKEL T, Lathe G . The effect of 17-alpha-ethinyl-substituted steroids on adenosine triphosphatases of rat liver plasma membrane. Biochem J. 1970; 118(1):187-9. PMC: 1179096. DOI: 10.1042/bj1180187. View

13.

Poupon R, Dumont M, Erlinger S . Hepatic storage and biliary transport maximum of taurocholate and taurochenodeoxycholate in the dog. Eur J Clin Invest. 1976; 6(6):431-7. DOI: 10.1111/j.1365-2362.1976.tb00539.x. View

14.

Strange R, Nimmo I, PERCY-ROBB I . Binding of bile acids to 100000g supernatants from rat liver. Biochem Soc Trans. 1976; 4(6):1102-3. DOI: 10.1042/bst0041102. View

15.

Schwarz L, Schwenk M, Pfaff E, Greim H . Excretion of taurocholate from isolated hepatocytes. Eur J Biochem. 1976; 71(2):369-73. DOI: 10.1111/j.1432-1033.1976.tb11123.x. View

16.

Anwer M, Gronwall R . A compartmental model for bilirubin kinetics in isolated perfused rat liver. Can J Physiol Pharmacol. 1976; 54(3):277-86. DOI: 10.1139/y76-041. View

17.

Anwer M, Kroker R, HEGNER D . Bile acids secretion and synthesis by isolated rat hepatocytes. Biochem Biophys Res Commun. 1975; 64(2):603-9. DOI: 10.1016/0006-291x(75)90364-2. View