Skip to main content
PMC home page
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1997 Jul-Aug;70(4):341–346.

Effects of bile acids on hepatocellular signaling and secretion.

U Beuers 1
PMCID: PMC2589332  PMID: 9626754

Abstract

Bile acids modulate hepatocellular signaling pathways in vitro at physiological concentrations. The present paper provides a brief overview of the effects of bile acids on three key messengers in liver cells: cytosolic free calcium, protein kinase A and protein kinase C.

Full text

PDF
341

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anwer M. S., Engelking L. R., Nolan K., Sullivan D., Zimniak P., Lester R. Hepatotoxic bile acids increase cytosolic Ca++ activity of isolated rat hepatocytes. Hepatology. 1988 Jul-Aug;8(4):887–891. doi: 10.1002/hep.1840080430. [DOI] [PubMed] [Google Scholar]
  2. Anwer M. S., Little J. M., Oelberg D. G., Zimniak P., Lester R. Effect of bile acids on calcium efflux from isolated rat hepatocytes and perfused rat livers. Proc Soc Exp Biol Med. 1989 Jun;191(2):147–152. doi: 10.3181/00379727-191-42900. [DOI] [PubMed] [Google Scholar]
  3. Barr V. A., Hubbard A. L. Newly synthesized hepatocyte plasma membrane proteins are transported in transcytotic vesicles in the bile duct-ligated rat. Gastroenterology. 1993 Aug;105(2):554–571. doi: 10.1016/0016-5085(93)90734-t. [DOI] [PubMed] [Google Scholar]
  4. Benedetti A., Strazzabosco M., Ng O. C., Boyer J. L. Regulation of activity and apical targeting of the Cl-/HCO3- exchanger in rat hepatocytes. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):792–796. doi: 10.1073/pnas.91.2.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beuers U., Nathanson M. H., Boyer J. L. Effects of tauroursodeoxycholic acid on cytosolic Ca2+ signals in isolated rat hepatocytes. Gastroenterology. 1993 Feb;104(2):604–612. doi: 10.1016/0016-5085(93)90433-d. [DOI] [PubMed] [Google Scholar]
  6. Beuers U., Nathanson M. H., Isales C. M., Boyer J. L. Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. J Clin Invest. 1993 Dec;92(6):2984–2993. doi: 10.1172/JCI116921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beuers U., Spengler U., Kruis W., Aydemir U., Wiebecke B., Heldwein W., Weinzierl M., Pape G. R., Sauerbruch T., Paumgartner G. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial. Hepatology. 1992 Sep;16(3):707–714. doi: 10.1002/hep.1840160315. [DOI] [PubMed] [Google Scholar]
  8. Beuers U., Thiel M., Bardenheuer H., Paumgartner G. Tauroursodeoxycholic acid inhibits the cytosolic Ca++ increase in human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine. Biochem Biophys Res Commun. 1990 Sep 28;171(3):1115–1121. doi: 10.1016/0006-291x(90)90800-3. [DOI] [PubMed] [Google Scholar]
  9. Beuers U., Throckmorton D. C., Anderson M. S., Isales C. M., Thasler W., Kullak-Ublick G. A., Sauter G., Koebe H. G., Paumgartner G., Boyer J. L. Tauroursodeoxycholic acid activates protein kinase C in isolated rat hepatocytes. Gastroenterology. 1996 May;110(5):1553–1563. doi: 10.1053/gast.1996.v110.pm8613063. [DOI] [PubMed] [Google Scholar]
  10. Bouscarel B., Fromm H., Nussbaum R. Ursodeoxycholate mobilizes intracellular Ca2+ and activates phosphorylase a in isolated hepatocytes. Am J Physiol. 1993 Feb;264(2 Pt 1):G243–G251. doi: 10.1152/ajpgi.1993.264.2.G243. [DOI] [PubMed] [Google Scholar]
  11. Bouscarel B., Gettys T. W., Fromm H., Dubner H. Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC. Am J Physiol. 1995 Feb;268(2 Pt 1):G300–G310. doi: 10.1152/ajpgi.1995.268.2.G300. [DOI] [PubMed] [Google Scholar]
  12. Boyer J. L., Soroka C. J. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology. 1995 Nov;109(5):1600–1611. doi: 10.1016/0016-5085(95)90649-5. [DOI] [PubMed] [Google Scholar]
  13. Bruck R., Nathanson M. H., Roelofsen H., Boyer J. L. Effects of protein kinase C and cytosolic Ca2+ on exocytosis in the isolated perfused rat liver. Hepatology. 1994 Oct;20(4 Pt 1):1032–1040. doi: 10.1002/hep.1840200436. [DOI] [PubMed] [Google Scholar]
  14. Burgoyne R. D., Morgan A. Regulated exocytosis. Biochem J. 1993 Jul 15;293(Pt 2):305–316. doi: 10.1042/bj2930305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Colombo C., Crosignani A., Assaisso M., Battezzati P. M., Podda M., Giunta A., Zimmer-Nechemias L., Setchell K. D. Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a dose-response study. Hepatology. 1992 Oct;16(4):924–930. doi: 10.1002/hep.1840160412. [DOI] [PubMed] [Google Scholar]
  16. Combettes L., Berthon B., Doucet E., Erlinger S., Claret M. Bile acids mobilise internal Ca2+ independently of external Ca2+ in rat hepatocytes. Eur J Biochem. 1990 Jul 5;190(3):619–623. doi: 10.1111/j.1432-1033.1990.tb15617.x. [DOI] [PubMed] [Google Scholar]
  17. Combettes L., Berthon B., Doucet E., Erlinger S., Claret M. Characteristics of bile acid-mediated Ca2+ release from permeabilized liver cells and liver microsomes. J Biol Chem. 1989 Jan 5;264(1):157–167. [PubMed] [Google Scholar]
  18. Combettes L., Dumont M., Berthon B., Erlinger S., Claret M. Release of calcium from the endoplasmic reticulum by bile acids in rat liver cells. J Biol Chem. 1988 Feb 15;263(5):2299–2303. [PubMed] [Google Scholar]
  19. Corasanti J. G., Smith N. D., Gordon E. R., Boyer J. L. Protein kinase C agonists inhibit bile secretion independently of effects on the microcirculation in the isolated perfused rat liver. Hepatology. 1989 Jul;10(1):8–13. doi: 10.1002/hep.1840100103. [DOI] [PubMed] [Google Scholar]
  20. Exton J. H. Role of phosphoinositides in the regulation of liver function. Hepatology. 1988 Jan-Feb;8(1):152–166. doi: 10.1002/hep.1840080129. [DOI] [PubMed] [Google Scholar]
  21. Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
  22. Galle P. R., Theilmann L., Raedsch R., Otto G., Stiehl A. Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology. 1990 Sep;12(3 Pt 1):486–491. doi: 10.1002/hep.1840120307. [DOI] [PubMed] [Google Scholar]
  23. Heuman D. M., Mills A. S., McCall J., Hylemon P. B., Pandak W. M., Vlahcevic Z. R. Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. Gastroenterology. 1991 Jan;100(1):203–211. doi: 10.1016/0016-5085(91)90602-h. [DOI] [PubMed] [Google Scholar]
  24. Hug H., Sarre T. F. Protein kinase C isoenzymes: divergence in signal transduction? Biochem J. 1993 Apr 15;291(Pt 2):329–343. doi: 10.1042/bj2910329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Häussinger D., Saha N., Hallbrucker C., Lang F., Gerok W. Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver. Biochem J. 1993 Apr 15;291(Pt 2):355–360. doi: 10.1042/bj2910355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jacquemin E., Hermans D., Myara A., Habes D., Debray D., Hadchouel M., Sokal E. M., Bernard O. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology. 1997 Mar;25(3):519–523. doi: 10.1002/hep.510250303. [DOI] [PubMed] [Google Scholar]
  27. Larkin J. M., Palade G. E. Transcytotic vesicular carriers for polymeric IgA receptors accumulate in rat hepatocytes after bile duct ligation. J Cell Sci. 1991 Feb;98(Pt 2):205–216. doi: 10.1242/jcs.98.2.205. [DOI] [PubMed] [Google Scholar]
  28. Lindor K. D., Therneau T. M., Jorgensen R. A., Malinchoc M., Dickson E. R. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology. 1996 May;110(5):1515–1518. doi: 10.1053/gast.1996.v110.pm8613058. [DOI] [PubMed] [Google Scholar]
  29. Nakamura S., Nishizuka Y. Lipid mediators and protein kinase C activation for the intracellular signaling network. J Biochem. 1994 Jun;115(6):1029–1034. doi: 10.1093/oxfordjournals.jbchem.a124451. [DOI] [PubMed] [Google Scholar]
  30. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992 Oct 23;258(5082):607–614. doi: 10.1126/science.1411571. [DOI] [PubMed] [Google Scholar]
  31. Poupon R., Poupon R. E. Ursodeoxycholic acid therapy of chronic cholestatic conditions in adults and children. Pharmacol Ther. 1995 Apr;66(1):1–15. doi: 10.1016/0163-7258(94)00073-c. [DOI] [PubMed] [Google Scholar]
  32. Roelofsen H., Ottenhoff R., Oude Elferink R. P., Jansen P. L. Hepatocanalicular organic-anion transport is regulated by protein kinase C. Biochem J. 1991 Sep 15;278(Pt 3):637–641. doi: 10.1042/bj2780637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stiehl A., Walker S., Stiehl L., Rudolph G., Hofmann W. J., Theilmann L. Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. J Hepatol. 1994 Jan;20(1):57–64. doi: 10.1016/s0168-8278(05)80467-2. [DOI] [PubMed] [Google Scholar]
  34. Stravitz R. T., Rao Y. P., Vlahcevic Z. R., Gurley E. C., Jarvis W. D., Hylemon P. B. Hepatocellular protein kinase C activation by bile acids: implications for regulation of cholesterol 7 alpha-hydroxylase. Am J Physiol. 1996 Aug;271(2 Pt 1):G293–G303. doi: 10.1152/ajpgi.1996.271.2.G293. [DOI] [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES