Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Nov 15;216(2):409–414. doi: 10.1042/bj2160409

Abnormal secretion of proteins into bile from colchicine-treated isolated perfused rat livers.

S G Barnwell, R Coleman
PMCID: PMC1152518  PMID: 6661206

Abstract

The microtubule poison, colchicine, caused an abnormal output of a variety of proteins into rat bile. After 3 h of exposure to the drug, livers were isolated and perfused with media of defined protein composition. There was no essential change in permeability of the hepatobiliary system to proteins (e.g. bovine serum albumin) entering bile from the perfusion fluid. The rat (serum) albumin and fibrinogen that were secreted into bile from colchicine-treated livers were probably derived from the hepatocytes. Disruption of the microtubular system reduces the secretion of proteins at the sinusoidal face of the hepatocyte and results in an accumulation of secretory vesicles in the cytoplasm. It is suggested that under these conditions some of the vesicles discharge their contents into the bile canaliculus.

Full text

PDF
409

Images in this article

412-1EXPLANATION OF PLATE 1
on p.412-1

Selected References

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

  1. Barnwell S. G., Lowe P. J., Coleman R. Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers. Biochem J. 1983 Oct 15;216(1):107–111. doi: 10.1042/bj2160107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bode J. C., Zelder O., Neuberger H. O. Effect of taurocholate, dehydrocholate and secretin on biliary output of alkaline phosphatase and GOT. Helv Med Acta. 1973 Sep;37(2):143–151. [PubMed] [Google Scholar]
  3. Coleman R., Iqbal S., Godfrey P. P., Billington D. Membranes and bile formation. Composition of several mammalian biles and their membrane-damaging properties. Biochem J. 1979 Jan 15;178(1):201–208. doi: 10.1042/bj1780201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dive C., Heremans J. F. Nature and origin of the proteins of bile. I. A comparative analysis of serum and bile proteins in man. Eur J Clin Invest. 1974 Aug;4(4):235–239. doi: 10.1111/j.1365-2362.1974.tb00398.x. [DOI] [PubMed] [Google Scholar]
  5. Dive C., Nadalini R. A., Vaerman J. P., Heremans J. F. Origin and nature of the proteins of bile. II. A comparative analysis of serum, hepatic lymph and bile proteins in the dog. Eur J Clin Invest. 1974 Aug;4(4):241–246. doi: 10.1111/j.1365-2362.1974.tb00399.x. [DOI] [PubMed] [Google Scholar]
  6. Evans W. H., Flint N. A., Vischer P. Biogenesis of hepatocyte plasma-membrane domains. Incorporation of (3H)fucose into plasma-membrane and golgi-apparatus glycoproteins. Biochem J. 1980 Dec 15;192(3):903–910. doi: 10.1042/bj1920903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Feldmann G., Maurice M., Sapin C., Benhamou J. P. Inhibition by colchicine of fibrinogen translocation in hepatocytes. J Cell Biol. 1975 Oct;67(1):237–243. doi: 10.1083/jcb.67.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Godfrey P. P., Lembra L., Coleman R. Effects of colchicine and vinblastine on output of proteins into bile. Biochem J. 1982 Oct 15;208(1):153–157. doi: 10.1042/bj2080153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Godfrey P. P., Warner M. J., Coleman R. Enzymes and proteins in bile. Variations in output in rat cannula bile during and after depletion of the bile-salt pool. Biochem J. 1981 Apr 15;196(1):11–16. doi: 10.1042/bj1960011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hatoff D. E., Hardison W. G. Bile acid-dependent secretion of alkaline phosphatase in rat bile. Hepatology. 1982 Jul-Aug;2(4):433–439. doi: 10.1002/hep.1840020407. [DOI] [PubMed] [Google Scholar]
  11. Holdsworth G., Coleman R. Enzyme profiles of mammalian bile. Biochim Biophys Acta. 1975 Apr 21;389(1):47–50. doi: 10.1016/0005-2736(75)90384-3. [DOI] [PubMed] [Google Scholar]
  12. LaRusso N. F., Fowler S. Coordinate secretion of acid hydrolases in rat bile. J Clin Invest. 1979 Oct;64(4):948–954. doi: 10.1172/JCI109561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Le Marchand Y., Patzelt C., Assimacopoulos-Jeannet F., Loten E. G., Jeanrenaud B. Evidence for a role of the microtubular system in the secretion of newly synthesized albumin and other proteins by the liver. J Clin Invest. 1974 Jun;53(6):1512–1517. doi: 10.1172/JCI107701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Le Marchand Y., Singh A., Assimacopoulos-Jeannet F., Orci L., Rouiller C., Jeanrenaud B. A role for the microtubular system in the release of very low density lipoproteins by perfused mouse livers. J Biol Chem. 1973 Oct 10;248(19):6862–6870. [PubMed] [Google Scholar]
  15. Lemaître-Coelho I., Jackson G. D., Vaerman J. P. Rat bile as a convenient source of secretory IgA and free secretory component. Eur J Immunol. 1977 Aug;7(8):588–590. doi: 10.1002/eji.1830070818. [DOI] [PubMed] [Google Scholar]
  16. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  17. Mullock B. M., Hinton R. H. The relation of bile proteins to serum and liver plasma membrane [proceedings]. Biochem Soc Trans. 1978;6(1):274–276. doi: 10.1042/bst0060274. [DOI] [PubMed] [Google Scholar]
  18. Mullock B. M., Jones R. S., Peppard J., Hinton R. H. Effect of colchicine on the transfer of IgA across hepatocytes into bile in isolated perfused rat livers. FEBS Lett. 1980 Nov 3;120(2):278–282. doi: 10.1016/0014-5793(80)80316-4. [DOI] [PubMed] [Google Scholar]
  19. Oda K., Ikehara Y. Inhibitory effect of colchicine on translocation of alkaline phosphatase to the plasma membrane concomitant to its induction in rat liver. Biochim Biophys Acta. 1981 Jan 22;640(2):398–408. doi: 10.1016/0005-2736(81)90465-x. [DOI] [PubMed] [Google Scholar]
  20. Orci L., Le Marchand Y., Singh A., Assimacopoulos-Jeannet F., Rouiller C., Jeanrenaud B. Letter: Role of microtubules in lipoprotein secretion by the liver. Nature. 1973 Jul 6;244(5410):30–32. doi: 10.1038/244030a0. [DOI] [PubMed] [Google Scholar]
  21. Peters T., Jr Biosynthesis of rat serum albumin. VII. Effects observed in liver slices. Am J Physiol. 1973 Jun;224(6):1363–1368. doi: 10.1152/ajplegacy.1973.224.6.1363. [DOI] [PubMed] [Google Scholar]
  22. Redman C. M., Banerjee D., Howell K., Palade G. E. Colchicine inhibition of plasma protein release from rat hepatocytes. J Cell Biol. 1975 Jul;66(1):42–59. doi: 10.1083/jcb.66.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stein O., Sanger L., Stein Y. Colchicine-induced inhibition of lipoprotein and protein secretion into the serum and lack of interference with secretion of biliary phospholipids and cholesterol by rat liver in vivo. J Cell Biol. 1974 Jul;62(1):90–103. doi: 10.1083/jcb.62.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thomas P. Studies on the mechanisms of biliary excretion of circulating glycoproteins. The carcinoembryonic antigen. Biochem J. 1980 Dec 15;192(3):837–843. doi: 10.1042/bj1920837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thomas P., Toth C. A., Zamcheck N. The mechanism of biliary excretion of alpha 1-acid glycoprotein in the rat: evidence for a molecular weight-dependent, nonreceptor-mediated pathway. Hepatology. 1982 Nov-Dec;2(6):800–803. doi: 10.1002/hep.1840020610. [DOI] [PubMed] [Google Scholar]
  26. Whittaker J., Hammond V. A., Alberti K. G. The effects of colchicine on insulin binding to isolated rat hepatocytes. Biochem Soc Trans. 1981 Feb;9(1):88–89. doi: 10.1042/bst0090088. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES