Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 May 15;212(2):271–278. doi: 10.1042/bj2120271

Decreased flux through pyruvate dehydrogenase during calcium ion movements induced by vasopressin, alpha-adrenergic agonists and the ionophore A23187 in perfused rat liver.

H Sies, P Graf, D Crane
PMCID: PMC1152044  PMID: 6136270

Abstract

Vasopressin or alpha-adrenergic agents such as phenylephrine or adrenaline, but not glucagon, elicited an initial decrease in flux through pyruvate dehydrogenase assayed by 14CO2 production from [1-14C]pyruvate in perfused rat liver. This rapid decrease in 14CO2 production was maximal within 1-2 min of exposure, concomitant with a rise in effluent pyruvate concentration: a subsequent return towards initial values in both parameters was completed well before 5 min. This time course was superposed with Ca2+ efflux from perfused liver, maximal (at 116 nmol/min per g wet wt. of liver) at 1-2 min of exposure. The percentage of the active (dephospho) form of pyruvate dehydrogenase was not decreased at 2 min of exposure. The effect on flux through pyruvate dehydrogenase by phenylephrine was abolished by prazosine, phentolamine or phenoxybenzamine. Ionophore A23187 also caused a depression in 14CO2 production from [1-14C]pyruvate and a rise in effluent pyruvate concentration, but this effect was stable for longer times, and it was delayed when Ca2+ was omitted from the perfusion medium. Responses of phenylephrine and A23187 were not additive. The results demonstrate that under the experimental conditions employed in intact perfused liver, the mitochondrial multienzyme system of pyruvate dehydrogenase is sensitive to vasopressin, alpha-adrenergic agents and A23187. The similar time course in Ca2+ efflux may be indicative of the involvement of Ca2+ in mediating this effect.

Full text

PDF
278

Selected References

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

  1. Althaus-Salzmann M., Carafoli E., Jakob A. Ca2+, K+ redistributions and alpha-adrenergic activation of glycogenolysis in perfused rat livers. Eur J Biochem. 1980 May;106(1):241–248. doi: 10.1111/j.1432-1033.1980.tb06015.x. [DOI] [PubMed] [Google Scholar]
  2. Babcock D. F., Chen J. L., Yip B. P., Lardy H. A. Evidence for mitochondrial localization of the hormone-responsive pool of Ca2+ in isolated hepatocytes. J Biol Chem. 1979 Sep 10;254(17):8117–8120. [PubMed] [Google Scholar]
  3. Blackmore P. F., Brumley F. T., Marks J. L., Exton J. H. Studies on alpha-adrenergic activation of hepatic glucose output. Relationship between alpha-adrenergic stimulation of calcium efflux and activation of phosphorylase in isolated rat liver parenchymal cells. J Biol Chem. 1978 Jul 25;253(14):4851–4858. [PubMed] [Google Scholar]
  4. Blackmore P. F., Dehaye J. P., Exton J. H. Studies on alpha-adrenergic activation of hepatic glucose output. The role of mitochondrial calcium release in alpha-adrenergic activation of phosphorylase in perfused rat liver. J Biol Chem. 1979 Aug 10;254(15):6945–6950. [PubMed] [Google Scholar]
  5. Chen J. L., Babcock D. F., Lardy H. A. Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes. Proc Natl Acad Sci U S A. 1978 May;75(5):2234–2238. doi: 10.1073/pnas.75.5.2234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coll K. E., Joseph S. K., Corkey B. E., Williamson J. R. Determination of the matrix free Ca2+ concentration and kinetics of Ca2+ efflux in liver and heart mitochondria. J Biol Chem. 1982 Aug 10;257(15):8696–8704. [PubMed] [Google Scholar]
  7. Davis R. J., Martin B. R. The effect of alpha-adrenergic agonists on the membrane potential of fat-cell mitochondria in situ. Biochem J. 1982 Sep 15;206(3):619–626. doi: 10.1042/bj2060619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denton R. M., McCormack J. G. On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Lett. 1980 Sep 22;119(1):1–8. doi: 10.1016/0014-5793(80)80986-0. [DOI] [PubMed] [Google Scholar]
  9. Denton R. M., Randle P. J., Martin B. R. Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem J. 1972 Jun;128(1):161–163. doi: 10.1042/bj1280161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Exton J. H. Mechanisms involved in alpha-adrenergic phenomena: role of calcium ions in actions of catecholamines in liver and other tissues. Am J Physiol. 1980 Jan;238(1):E3–12. doi: 10.1152/ajpendo.1980.238.1.E3. [DOI] [PubMed] [Google Scholar]
  11. Garrison J. C., Borland M. K. Regulation of mitochondrial pyruvate carboxylation and gluconeogenesis in rat hepatocytes via an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism. J Biol Chem. 1979 Feb 25;254(4):1129–1133. [PubMed] [Google Scholar]
  12. Hems D. A., McCormack J. G., Denton R. M. Activation of pyruvate dehydrogenase in the perfused rat liver by vasopressin. Biochem J. 1978 Nov 15;176(2):627–629. doi: 10.1042/bj1760627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Häussinger D., Weiss L., Sies H. Activation of pyruvate dehydrogenase during metabolism of ammonium ions in hemoglobin-free perfused rat liver. Eur J Biochem. 1975 Apr 1;52(3):421–431. doi: 10.1111/j.1432-1033.1975.tb04010.x. [DOI] [PubMed] [Google Scholar]
  14. Kessar P., Crompton M. The alpha-adrenergic-mediated activation of Ca2+ influx into cardiac mitochondria. A possible mechanism for the regulation of intramitochondrial free CA2+. Biochem J. 1981 Nov 15;200(2):379–388. doi: 10.1042/bj2000379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Murphy E., Coll K., Rich T. L., Williamson J. R. Hormonal effects on calcium homeostasis in isolated hepatocytes. J Biol Chem. 1980 Jul 25;255(14):6600–6608. [PubMed] [Google Scholar]
  16. Patel T. B., Debuysere M. S., Scholz R., Olson M. S. The regulation of the pyruvate dehydrogenase complex in the perfused rat liver: a role for the mitochondrial monocarboxylate translocator. Arch Biochem Biophys. 1982 Feb;213(2):573–584. doi: 10.1016/0003-9861(82)90586-0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Reinhart P. H., Taylor W. M., Bygrave F. L. Studies on alpha-adrenergic-induced respiration and glycogenolysis in perfused rat liver. J Biol Chem. 1982 Feb 25;257(4):1906–1912. [PubMed] [Google Scholar]
  19. Roche T. E., Cate R. L. Purification of porcine liver pyruvate dehydrogenase complex and characterization of its catalytic and regulatory properties. Arch Biochem Biophys. 1977 Oct;183(2):664–677. doi: 10.1016/0003-9861(77)90400-3. [DOI] [PubMed] [Google Scholar]
  20. Sies H., Graf P., Estrela J. M. Hepatic calcium efflux during cytochrome P-450-dependent drug oxidations at the endoplasmic reticulum in intact liver. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3358–3362. doi: 10.1073/pnas.78.6.3358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sies H. The use of perfusion of liver and other organs for the study of microsomal electron-transport and cytochrome P-450 systems. Methods Enzymol. 1978;52:48–59. doi: 10.1016/s0076-6879(78)52005-3. [DOI] [PubMed] [Google Scholar]
  22. Sugano T., Shiota M., Khono H., Shimada M., Oshino N. Effects of calcium ions on the activation of gluconeogenesis by norepinephrine in perfused rat liver. J Biochem. 1980 Feb;87(2):465–472. doi: 10.1093/oxfordjournals.jbchem.a132766. [DOI] [PubMed] [Google Scholar]
  23. TABOR H., MEHLER A. H., STADTMAN E. R. The enzymatic acetylation of amines. J Biol Chem. 1953 Sep;204(1):127–138. [PubMed] [Google Scholar]
  24. Walajtys E. I., Gottesman D. P., Williamson J. R. Regulation of pyruvate dehydrogenase in rat liver mitochondria by phosphorylation-dephosphorylation. J Biol Chem. 1974 Mar 25;249(6):1857–1865. [PubMed] [Google Scholar]
  25. Wieland O. H., Patzelt C., Löffler G. Active and inactive forms of pyruvate dehydrogenase in rat liver. Effect of starvation and refeeding and of insulin treatment on pyruvate-dehydrogenase interconversion. Eur J Biochem. 1972 Apr 11;26(3):426–433. doi: 10.1111/j.1432-1033.1972.tb01783.x. [DOI] [PubMed] [Google Scholar]
  26. Williamson J. R., Cooper R. H., Hoek J. B. Role of calcium in the hormonal regulation of liver metabolism. Biochim Biophys Acta. 1981 Dec 30;639(3-4):243–295. doi: 10.1016/0304-4173(81)90012-4. [DOI] [PubMed] [Google Scholar]
  27. Yip B. P., Lardy H. A. The role of calcium in the stimulation of gluconeogenesis by catecholamines. Arch Biochem Biophys. 1981 Dec;212(2):370–377. doi: 10.1016/0003-9861(81)90377-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES