Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1994 Jul 1;301(Pt 1):187–192. doi: 10.1042/bj3010187

The synergistic action (cross-talk) of glucagon and vasopressin induces early bile flow and plasma-membrane calcium fluxes in the perfused rat liver.

A Karjalainen 1, F L Bygrave 1
PMCID: PMC1137160  PMID: 8037669

Abstract

A study was made of the initial responses of perfusate Ca2+ fluxes and bile flow to Ca(2+)-mobilizing agonists, following refinements to the methods for analysing these parameters in the perfused rat liver. Net Ca2+ efflux induced by vasopressin commences at 15 s, reaches a maximal rate at 35 s and declines to zero by 55 s, when Ca2+ influx commences. Vasopressin-induced increases in bile flow commence by 20 s, attain a maximal rate by 35 s and begin to decline at 50 s, to reach basal values by 90 s. Concomitant administration of glucagon modifies each of these actions of vasopressin in the following ways: it decreases by 5 s the time of onset of net Ca2+ efflux, and the time and magnitude of such efflux, and the time of onset of bile flow is decreased to 15 s, and the flow reaches maximal rates by 30 s. When the alpha 1-adrenergic agonist phenylephrine is used in place of vasopressin, Ca2+ efflux commences at 17-18 s and is greater in magnitude; little bile flow is induced by this agonist. Glucagon modifies the action of phenylephrine in the following ways: the onset of Ca2+ efflux is brought forward by 2-3 s, it is of lower magnitude and Ca2+ influx begins by 45 s; bile flow commences by 15-20 s, and reaches a maximum at 30 s, where the rate is much greater than in the absence of glucagon; this rate gradually declines to be near basal by 80 s. The onset of agonist-induced oxygen uptake was also brought forward by the co-administration of glucagon. Comparison of agonist-induced plasma-membrane Ca2+ fluxes and bile flow (with or without glucagon administration) suggests that correlations can be made between net Ca2+ fluxes and the transient increases seen in bile flow.

Full text

PDF
187

Selected References

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

  1. Altin J. G., Bygrave F. L. Synergistic stimulation of Ca2+ uptake by glucagon and Ca2+-mobilizing hormones in the perfused rat liver. A role for mitochondria in long-term Ca2+ homoeostasis. Biochem J. 1986 Sep 15;238(3):653–661. doi: 10.1042/bj2380653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altin J. G., Bygrave F. L. The Ca2+-mobilizing actions of vasopressin and angiotensin differ from those of the alpha-adrenergic agonist phenylephrine in the perfused rat liver. Biochem J. 1985 Dec 15;232(3):911–917. doi: 10.1042/bj2320911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Biden T. J., Browne C. L. Cross-talk between muscarinic- and adenosine-receptor signalling in the regulation of cytosolic free Ca2+ and insulin secretion. Biochem J. 1993 Aug 1;293(Pt 3):721–728. doi: 10.1042/bj2930721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bruck R., Haddad P., Graf J., Boyer J. L. Regulatory volume decrease stimulates bile flow, bile acid excretion, and exocytosis in isolated perfused rat liver. Am J Physiol. 1992 May;262(5 Pt 1):G806–G812. doi: 10.1152/ajpgi.1992.262.5.G806. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Bygrave F. L., Benedetti A. Calcium: its modulation in liver by cross-talk between the actions of glucagon and calcium-mobilizing agonists. Biochem J. 1993 Nov 15;296(Pt 1):1–14. doi: 10.1042/bj2960001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bygrave F. L., Karjalainen A., Hamada Y. Crosstalk between calcium- and cyclic AMP-mediated signalling systems and the short-term modulation of bile flow in normal and cholestatic rat liver. Cell Signal. 1994 Jan;6(1):1–9. doi: 10.1016/0898-6568(94)90055-8. [DOI] [PubMed] [Google Scholar]
  10. Charest R., Blackmore P. F., Berthon B., Exton J. H. Changes in free cytosolic Ca2+ in hepatocytes following alpha 1-adrenergic stimulation. Studies on Quin-2-loaded hepatocytes. J Biol Chem. 1983 Jul 25;258(14):8769–8773. [PubMed] [Google Scholar]
  11. Coleman R. Biochemistry of bile secretion. Biochem J. 1987 Jun 1;244(2):249–261. doi: 10.1042/bj2440249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Combettes L., Berthon B., Binet A., Claret M. Glucagon and vasopressin interactions on Ca2+ movements in isolated hepatocytes. Biochem J. 1986 Aug 1;237(3):675–683. doi: 10.1042/bj2370675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Denton R. M., McCormack J. G. Ca2+ transport by mammalian mitochondria and its role in hormone action. Am J Physiol. 1985 Dec;249(6 Pt 1):E543–E554. doi: 10.1152/ajpendo.1985.249.6.E543. [DOI] [PubMed] [Google Scholar]
  16. Duddy S. K., Kass G. E., Orrenius S. Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes. J Biol Chem. 1989 Dec 15;264(35):20863–20866. [PubMed] [Google Scholar]
  17. Hallbrucker C., Lang F., Gerok W., Häussinger D. Cell swelling increases bile flow and taurocholate excretion into bile in isolated perfused rat liver. Biochem J. 1992 Feb 1;281(Pt 3):593–595. doi: 10.1042/bj2810593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamada Y., Karjalainen A., Setchell B. A., Millard J. E., Bygrave F. L. Acute effects of cholestatic and choleretic bile salts on vasopressin- and glucagon-induced hepato-biliary calcium fluxes in the perfused rat liver. Biochem J. 1992 Apr 15;283(Pt 2):575–581. doi: 10.1042/bj2830575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hamada Y., Karjalainen A., Setchell B. A., Millard J. E., Bygrave F. L. Concomitant stimulation by vasopressin of biliary and perfusate calcium fluxes in the perfused rat liver. Biochem J. 1992 Jan 15;281(Pt 2):387–392. doi: 10.1042/bj2810387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hardison W. G., Dalle-Molle E., Gosink E., Lowe P. J., Steinbach J. H., Yamaguchi Y. Function of rat hepatocyte tight junctions: studies with bile acid infusions. Am J Physiol. 1991 Jan;260(1 Pt 1):G167–G174. doi: 10.1152/ajpgi.1991.260.1.G167. [DOI] [PubMed] [Google Scholar]
  21. Hill C. E., Dawson A. P., Pryor J. S. Evidence for adrenergic control of transcellular calcium distribution in liver. Biochem J. 1985 Sep 15;230(3):733–737. doi: 10.1042/bj2300733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holz G. G., Habener J. F. Signal transduction crosstalk in the endocrine system: pancreatic beta-cells and the glucose competence concept. Trends Biochem Sci. 1992 Oct;17(10):388–393. doi: 10.1016/0968-0004(92)90006-u. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Häussinger D., Hallbrucker C., Saha N., Lang F., Gerok W. Cell volume and bile acid excretion. Biochem J. 1992 Dec 1;288(Pt 2):681–689. doi: 10.1042/bj2880681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Häussinger D., Lang F. Cell volume and hormone action. Trends Pharmacol Sci. 1992 Oct;13(10):371–373. doi: 10.1016/0165-6147(92)90114-l. [DOI] [PubMed] [Google Scholar]
  25. Kan K. S., Coleman R. The calcium ionophore A23187 increases the tight-junctional permeability in rat liver. Biochem J. 1988 Dec 15;256(3):1039–1041. doi: 10.1042/bj2561039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Krell H., Jaeschke H., Pfaff E. Regulation of canalicular bile formation by alpha-adrenergic action and by external ATP in the isolated perfused rat liver. Biochem Biophys Res Commun. 1985 Aug 30;131(1):139–145. doi: 10.1016/0006-291x(85)91781-4. [DOI] [PubMed] [Google Scholar]
  27. Llopis J., Kass G. E., Duddy S. K., Farell G. C., Gahm A., Orrenius S. Mobilization of the hormone-sensitive calcium pool increases hepatocyte tight junctional permeability in the perfused rat liver. FEBS Lett. 1991 Mar 11;280(1):84–86. doi: 10.1016/0014-5793(91)80209-l. [DOI] [PubMed] [Google Scholar]
  28. Lowe P. J., Miyai K., Steinbach J. H., Hardison W. G. Hormonal regulation of hepatocyte tight junctional permeability. Am J Physiol. 1988 Oct;255(4 Pt 1):G454–G461. doi: 10.1152/ajpgi.1988.255.4.G454. [DOI] [PubMed] [Google Scholar]
  29. McCormack J. G., Denton R. M. The role of intramitochondrial Ca2+ in the regulation of oxidative phosphorylation in mammalian tissues. Biochem Soc Trans. 1993 Aug;21(3):793–799. doi: 10.1042/bst0210793. [DOI] [PubMed] [Google Scholar]
  30. Nathanson M. H., Boyer J. L. Mechanisms and regulation of bile secretion. Hepatology. 1991 Sep;14(3):551–566. [PubMed] [Google Scholar]
  31. Nathanson M. H., Gautam A., Bruck R., Isales C. M., Boyer J. L. Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver. Hepatology. 1992 Jan;15(1):107–116. doi: 10.1002/hep.1840150119. [DOI] [PubMed] [Google Scholar]
  32. Owen C. A., Jr Isolated rat liver needs calcium to make bile. Proc Soc Exp Biol Med. 1977 Jul;155(3):314–317. doi: 10.3181/00379727-155-39797. [DOI] [PubMed] [Google Scholar]
  33. Reichen J., Berr F., Le M., Warren G. H. Characterization of calcium deprivation-induced cholestasis in the perfused rat liver. Am J Physiol. 1985 Jul;249(1 Pt 1):G48–G57. doi: 10.1152/ajpgi.1985.249.1.G48. [DOI] [PubMed] [Google Scholar]
  34. Reinhart P. H., Taylor W. M., Bygrave F. L. Calcium ion fluxes induced by the action of alpha-adrenergic agonists in perfused rat liver. Biochem J. 1982 Dec 15;208(3):619–630. doi: 10.1042/bj2080619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ruttner Z., Ligeti L., Reinlib L., Hines K., McLaughlin A. C. Monitoring of intracellular free calcium in perfused rat liver. Cell Calcium. 1993 Jun;14(6):465–472. doi: 10.1016/0143-4160(93)90005-q. [DOI] [PubMed] [Google Scholar]
  36. Sharma B. K., Bacon B. R., Britton R. S., Park C. H., Magiera C. J., O'Neill R., Dalton N., Smanik P., Speroff T. Prevention of hepatocyte injury and lipid peroxidation by iron chelators and alpha-tocopherol in isolated iron-loaded rat hepatocytes. Hepatology. 1990 Jul;12(1):31–39. doi: 10.1002/hep.1840120107. [DOI] [PubMed] [Google Scholar]
  37. Sáez J. C., Connor J. A., Spray D. C., Bennett M. V. Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2708–2712. doi: 10.1073/pnas.86.8.2708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Thibault N., Ballet F. Effect of bile acids on intracellular calcium in isolated rat hepatocyte couplets. Biochem Pharmacol. 1993 Jan 26;45(2):289–293. doi: 10.1016/0006-2952(93)90063-3. [DOI] [PubMed] [Google Scholar]
  39. Varin F., Huet P. M. Hepatic microcirculation in the perfused cirrhotic rat liver. J Clin Invest. 1985 Nov;76(5):1904–1912. doi: 10.1172/JCI112186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Watanabe S., Tomono M., Takeuchi M., Kitamura T., Hirose M., Miyazaki A., Namihisa T. Bile canalicular contraction in the isolated hepatocyte doublet is related to an increase in cytosolic free calcium ion concentration. Liver. 1988 Jun;8(3):178–183. doi: 10.1111/j.1600-0676.1988.tb00988.x. [DOI] [PubMed] [Google Scholar]
  41. Yamaguchi Y., Dalle-Molle E., Hardison W. G. Vasopressin and A23187 stimulate phosphorylation of myosin light chain-1 in isolated rat hepatocytes. Am J Physiol. 1991 Aug;261(2 Pt 1):G312–G319. doi: 10.1152/ajpgi.1991.261.2.G312. [DOI] [PubMed] [Google Scholar]
  42. vom Dahl S., Hallbrucker C., Lang F., Häussinger D. Regulation of cell volume in the perfused rat liver by hormones. Biochem J. 1991 Nov 15;280(Pt 1):105–109. doi: 10.1042/bj2800105. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES