Indirect evidence that intestinal bile salt absorption in rats and hamsters is under positive feedback control

Summary: Bile salts are reabsorbed from the intestine by active and passive transport mechanisms with great efficacy. Conflicting data do not allow to judge for certainty whether bile salt absorption is under negative or positive feedback control. To address this issue, we analyzed bile salt absorption in vivo along the entire intestinal tract of rats and hamsters that received intraduodenal bile salt infusions for 54 h following interruption of the enterohepatic circulation. Taurocholate absorption in rats was complete, even when unphysiologically high concentrations of taurocholate were given. The combined infusion of taurocholate together with potent inhibitors of bile salt synthesis such as deoxycholate, taurodeoxycholate or taurochenodeoxycholate, failed to inhibit bile salt absorption. In the hamster, taurochenodeoxycholate and taurocholate absorption was complete and could not be inhibited when given in supraphysiological concentrations. Finally, taurocholate absorption was not impaired when deoxycholic acid was infused. These results provide indirect evidence that bile salt absorption is under positive feedback control regulated by luminal bile salt concentrations.

Die intestinale Gallensäurenabsorption wird bei Ratte und Hamster durch einen positiven Feedback kontrolliert

Gallensäuren werden durch aktive und passive Transportmechanismen nahezu komplett aus dem Darm absorbiert. Ob die intestinale Gallensäurenabsorption einem negativen oder positiven Feedbackmechanismus unterliegt, ist derzeit unklar. Wir analysierten deshalb die intestinale Gallensäurenabsorption in vivo von Ratten und Hamster, die nach Unterbrechung der enterohepatischen Zirkulation eine intraduodenale Gallensäureninfusion für 54 h erhielten. Taurocholat wurde von Ratten vollständig absorbiert, sogar wenn unphysiologisch hohe Taurocholatkonzentrationen infundiert wurden. Die Taurocholatabsorption konnte durch die kombinierte Infusion von Taurocholat mit potenten Hemmern der Gallensäurensynthese wie Deoxycholat, Taurodeoxycholat oder Taurochenodeoxycholat nicht gehemmt werden. Beim Hamster war die Absorption von Taurochenodeoxycholat und Taurocholat vollständig und konnte auch durch unphysiologisch hohe Konzentrationen nicht gehemmt werden. Schließlich wurde die Taurocholatabsorption auch nicht durch die Infusion von Deoxycholsäure beeinträchtigt. Diese Ergebnisse liefern indirekte Hinweise, dass die intestinale Gallensäurenabsorption einer positiven Feedbackkontrolle, reguliert durch die luminale Gallensäurenkonzentration, unterliegt.

Key words

Bile Salts - Intestinal Absorption - Enterohepatic Circulation - Bile Fistula

Schlüsselwörter

Gallensalze - intestinale Absorption - enterohepatische Zirkulation - Gallefistel

References

• 1 Fuchs M, Stange E F. Metabolism of bile acids. Bircher J, Benhamou JP, McIntyre N, Rizzetto M, Rodes J Oxford Textbook of Clinical Hepatology Oxford University Press 1999 Oxford: 223-256
• 2 Dietschy J M. Mechanisms for the intestinal absorption of bile acids.  J Lipid Res. 1968;  9 297-309
• 3 Krag E, Phillips S F. Active and passive bile acid absorption in man.  J Clin Invest. 1974;  53 1686-1694
• 4 Amelsberg A, Schteingart C D, Ton-Nu H T, Hofmann A F. Carrier-mediated jejunal absorption of conjugated bile acids in the guinea pig.  Gastroenterology. 1996;  110 1098-1106
• 5 Walters H C, Craddock A L, Fusegawa H, Willingham M C, Dawson P A. Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.  Am J Physiol Gastrointest Liver Physiol. 2000;  279 G1188-G1200
• 6 Wong M H, Oelkers P, Craddock A L, Dawson P A. Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter.  J Biol Chem. 1994;  269 1340-1347
• 7 Craddock A L, Love M W, Daniel R W. et al . Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter.  Am J Physiol. 1998;  274 G157-G169
• 8 Wong M H, Oelkers P, Dawson P A. Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity.  J Biol Chem. 1995;  270 27 228-27 234
• 9 Stange E F, Scheibner J, Ditschuneit H. Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.  J Clin Invest. 1989;  84 173-180
• 10 Scheibner J, Fuchs M, Schiemann M, Stange E F. Deoxycholate and cholate modulate the source of cholesterol substrate for bile acid synthesis in the rat.  Hepatology. 1995;  21 529-538
• 11 Scheibner J, Fuchs M, Hörmann E, Stange E F. Complex feedback regulation of bile acid synthesis in the hamster: The role of newly synthesized cholesterol.  Hepatology. 1999;  30 230-237
• 12 Fuchs M, Scheibner J, Hörmann E, Tauber G, Stange E F. Enterohepatic circulation in hamsters with an extracorporeal bile duct.  J Lipid Res. 1992;  33 1383-1392
• 13 Stange E F, Scheibner J, Lutz C, Ditschuneit H. Feedback regulation of bile acid synthesis in the rat by dietary vs. intravenous cholate or taurocholate.  Hepatology. 1988;  8 879-886
• 14 Vonk R J, van Doorn A BD, Strubbe J H. Bile secretion and bile composition in the freely moving, unanaesthetized rat with a permanent biliary drainage: Influence of food intake on bile flow.  Clin Sci Mol Med. 1978;  55 253-259
• 15 Kuipers F, Havinga R, Bosschieter H. et al . Enterohepatic circulation in the rat.  Gastroenterology. 1985;  88 403-411
• 16 Weis E E, Barth C A. The extracorporeal bile duct: A new model for determination of bile flow and bile composition in the intact rat.  J Lipid Res. 1978;  19 856-862
• 17 Tietz P S, Thistle J L, Miller L J, LaRusso N F. Development and validation of a method for measuring the glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography.  J Chromatogr. 1984;  336 249-257
• 18 Scheibner J, Fuchs M, Schiemann M. et al . Bile acid synthesis from newly synthesized vs. performed cholesterol precursor pools in the rat.  Hepatology. 1993;  17 1095-1102
• 19 Marcus S N, Schteingart C D, Marquez M L. et al . Active absorption of conjugated bile acids in vivo. Kinetic parameters and molecular specificity of the ileal transport system in the rat.  Gastroenterology. 1991;  100 212-221
• 20 Lillienau J, Crombie D L, Munoz J. et al . Negative feedback regulation of the ileal bile acid transport system in rodents.  Gastroenterology. 1993;  104 38-46
• 21 Lillienau J. Zonal negative feedback regulation of active ileal bile acid transport in rodents. XIV. International Bile Acid Meeting, Falk Symposium Nr. 93 Freiburg; Abstract Booklet 1996: 42
• 22 Sauer P, Stiehl A, Fitscher B A. et al . Down-regulation of ileal bile acid absorption in bile-duct ligated rats.  J Hepatol. 2000;  33 2-8
• 23 Higgins J V, Paul J M, Dumaswala R, Heubi J E. Down-regulation of taurocholate transport by ileal BBM and liver BLM in biliary-diverted rats.  Am J Physiol. 1994;  267 G501-G507
• 24 Arrese M, Trauner M, Sacchiero R J, Crossman M W, Shneider B L. Neither intestinal sequestration of bile acids nor common bile duct ligation modulate the expression and function of the rat ileal bile acid transporter.  Hepatology. 1998;  28 1081-1087
• 25 Torchia E C, Cheema S K, Agellon L B. Coordinate regulation of bile acid biosynthetic and recovery pathways.  Biochem Biophys Res Commun. 1996;  225 128-133
• 26 Coppola C P, Gosche J R, Arrese M. et al . Molecular analysis of the adaptive response of intestinal bile acid transport after ileal resection in the rat.  Gastroenterology. 1998;  115 1172-1178
• 27 Stravitz R T, Sanyal A J, Pandak W M. et al . Induction of sodium-dependent bile acid transporter messenger RNA, protein, and activity in rat ileum by cholic acid.  Gastroenterology. 1997;  113 1599-1608
• 28 Dumaswala R, Berkowitz D, Setchell K DR, Heubi J E. Effect of fasting on the enterohepatic circulation of bile acids in rats.  Am J Physiol. 1994;  267 G836-G842
• 29 Cohen H, Bonorris G G, Marks J W, Schoenfield L J. Effect of zanchol and chenic acid on bile acid pool size and gallstones in hamsters.  Am J Med Sci. 1982;  283 23-31
• 30 Reynier M O, Montet J C, Gerolami A. et al . Comparative effects of cholic, chenodeoxycholic, and ursodeoxycholic acids on micellar solubilization and interstinal absorption of cholesterol.  J Lipid Res. 1981;  22 467-473
• 31 Mok H Y, Grundy S M. Cholesterol and bile acid absorption during bile acid therapy in obese subjects undergoing weight reduction.  Gastroenterology. 1980;  78 62-67
• 32 von Bergmann K, Epple-Gutsfeld M, Leiss O. Differences in the effects of chenodeoxycholic and ursodeoxycholic acid on biliary lipid secretion and bile acid synthesis in patients with gallstones.  Gastroenterology. 1984;  87 136-143
• 33 Dumaswala R, Berkowitz D, Heubi J E. Adaptive response of the enterohepatic circulation of bile acids to extrahepatic cholestasis.  Hepatology. 1996;  23 623-629
• 34 van Tilburg A JP, De Rooij F WM, van Blankenstein M, van den Berg J WO, Bosman-Jacobs E P. Na+-dependent bile acid transport in the ileum: The balance between diarrhea and constipation.  Gastroenterology. 1990;  98 25-32
• 35 Glasser J E, Weiner I M, Lack L. Comparative physiology of intestinal taurocholate transport.  Am J Physiol. 1965;  208 359-362
• 36 Sklan D, Budowski P, Hurwitz S. Site of bile acid absorption in the rat.  Lipids. 1976;  11 467-471
• 37 Mekhjian H S, Phillips S F, Hofmann A F. Colonic secretion of water and electrolytes induced by bile acids: Perfusion studies in man.  J Clin Invest. 1971;  50 1569-1577
• 38 Imray C HE, Radley S, Davis A. et al . Fecal unconjugated bile acids in patients with colorectal cancer or polyps.  Gut. 1992;  33 1239-1245

Address for correspondence ab 1.9.2001: