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. 1987 Feb 1;241(3):737–743. doi: 10.1042/bj2410737

Short-term stimulation of Na+-dependent amino acid transport by dibutyryl cyclic AMP in hepatocytes. Characteristics and partial mechanism.

S K Moule, N M Bradford, J D McGivan
PMCID: PMC1147625  PMID: 3036071

Abstract

The short-term protein-synthesis-independent stimulation of alanine transport in hepatocytes was further investigated. Cyclic AMP increased the Vmax. of alanine transport. Amino acid transport via systems A, ASC and N was stimulated. A good correlation was found between the initial rate of transport and the cell membrane potential as calculated from the distribution of Cl-. Cyclic AMP increased the rate of alanine transport, stimulated Na+/K+ ATPase (Na+/K+-transporting ATPase) activity and caused membrane hyperpolarization. The time courses and cyclic AMP dose-dependencies of all three effects were similar. Ouabain abolished the effect of cyclic AMP on Cl- distribution and on transport of alanine. The effect of cyclic AMP on alanine transport and Cl- distribution was mimicked by the antibiotic nigericin; the effect of nigericin was also abolished by ouabain. It is concluded that the effect of cyclic AMP on transport is mediated via membrane hyperpolarization. It is suggested that the primary action of cyclic AMP is to increase the activity of an electroneutral Na+/K+-exchange system in the liver cell plasma membrane, thus hyperpolarizing the membrane by stimulating the electrogenic Na+/K+ ATPase.

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Selected References

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

  1. Bakker-Grunwald T. Potassium permeability and volume control in isolated rat hepatocytes. Biochim Biophys Acta. 1983 Jun 10;731(2):239–242. doi: 10.1016/0005-2736(83)90014-7. [DOI] [PubMed] [Google Scholar]
  2. Bashford C. L., Pasternak C. A. Plasma membrane potential of Lettré cells does not depend on cation gradients but on pumps. J Membr Biol. 1984;79(3):275–284. doi: 10.1007/BF01871066. [DOI] [PubMed] [Google Scholar]
  3. Bradford N. M., Hayes M. R., McGivan J. D. The use of 36Cl- to measure cell plasma membrane potential in isolated hepatocytes--effects of cyclic AMP and bicarbonate ions. Biochim Biophys Acta. 1985 Apr 22;845(1):10–16. doi: 10.1016/0167-4889(85)90047-3. [DOI] [PubMed] [Google Scholar]
  4. Claret M., Mazet J. L. Ionic fluxes and permeabilities of cell membranes in rat liver. J Physiol. 1972 Jun;223(2):279–295. doi: 10.1113/jphysiol.1972.sp009847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edmondson J. W., Lumeng L. Biphasic stimulation of amino acid uptake by glucagon in hepatocytes. Biochem Biophys Res Commun. 1980 Sep 16;96(1):61–68. doi: 10.1016/0006-291x(80)91181-x. [DOI] [PubMed] [Google Scholar]
  6. Edmondson J. W., Lumeng L., Li T. K. Direct measurement of active transport systems for alanine in freshly isolated rat liver cells. Biochem Biophys Res Commun. 1977 Jun 6;76(3):751–757. doi: 10.1016/0006-291x(77)91564-9. [DOI] [PubMed] [Google Scholar]
  7. Edmondson J. W., Miller B. A., Lumeng L. Effect of glucagon on hepatic taurocholate uptake: relationship to membrane potential. Am J Physiol. 1985 Oct;249(4 Pt 1):G427–G433. doi: 10.1152/ajpgi.1985.249.4.G427. [DOI] [PubMed] [Google Scholar]
  8. Fafournoux P., Rémésy C., Demigné C. Control of alanine metabolism in rat liver by transport processes or cellular metabolism. Biochem J. 1983 Mar 15;210(3):645–652. doi: 10.1042/bj2100645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freidmann N., Dambach G. Effects of glucagon, 3',5'-AMP and 3',5'-GMP on ion fluxes and transmembrane potential in perfused livers of normal and adrenalectomized rats. Biochim Biophys Acta. 1973 May 11;307(2):399–403. doi: 10.1016/0005-2736(73)90105-3. [DOI] [PubMed] [Google Scholar]
  10. Geck P., Heinz E. Coupling in secondary transport. Effect of electrical potentials on the kinetics of ion linked co-transport. Biochim Biophys Acta. 1976 Aug 4;443(1):49–63. doi: 10.1016/0005-2736(76)90490-9. [DOI] [PubMed] [Google Scholar]
  11. Henderson P. J., McGivan J. D., Chappell J. B. The action of certain antibiotics on mitochondrial, erythrocyte and artificial phospholipid membranes. The role of induced proton permeability. Biochem J. 1969 Feb;111(4):521–535. doi: 10.1042/bj1110521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoek J. B., Nicholls D. G., Williamson J. R. Determination of the mitochondrial protonmotive force in isolated hepatocytes. J Biol Chem. 1980 Feb 25;255(4):1458–1464. [PubMed] [Google Scholar]
  13. Häussinger D., Soboll S., Meijer A. J., Gerok W., Tager J. M., Sies H. Role of plasma membrane transport in hepatic glutamine metabolism. Eur J Biochem. 1985 Nov 4;152(3):597–603. doi: 10.1111/j.1432-1033.1985.tb09237.x. [DOI] [PubMed] [Google Scholar]
  14. Ihlenfeldt M. J. Stimulation of Rb+ transport by glucagon in isolated rat hepatocytes. J Biol Chem. 1981 Mar 10;256(5):2213–2218. [PubMed] [Google Scholar]
  15. Joseph S. K., Bradford N. M., McGivan J. D. Characteristics of the transport of alanine, serine and glutamine across the plasma membrane of isolated rat liver cells. Biochem J. 1978 Dec 15;176(3):827–836. doi: 10.1042/bj1760827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Joseph S. K., McGivan J. D. The effect of ammonium chloride and glucagon on the metabolism of glutamine in isolated liver cells from starved rats. Biochim Biophys Acta. 1978 Sep 21;543(1):16–28. doi: 10.1016/0304-4165(78)90450-6. [DOI] [PubMed] [Google Scholar]
  17. Kilberg M. S. Amino acid transport in isolated rat hepatocytes. J Membr Biol. 1982;69(1):1–12. doi: 10.1007/BF01871236. [DOI] [PubMed] [Google Scholar]
  18. Kilberg M. S., Barber E. F., Handlogten M. E. Characteristics and hormonal regulation of amino acid transport system A in isolated rat hepatocytes. Curr Top Cell Regul. 1985;25:133–163. doi: 10.1016/b978-0-12-152825-6.50009-6. [DOI] [PubMed] [Google Scholar]
  19. McGivan J. D., Ramsell J. C., Lacey J. H. Stimulation of alanine transport and metabolism by dibutyryl cyclic AMP in the hepatocytes from fed rats. Assessment of transport as a potential rate-limiting step for alanine metabolism. Biochim Biophys Acta. 1981 Jun 22;644(2):295–304. doi: 10.1016/0005-2736(81)90387-4. [DOI] [PubMed] [Google Scholar]
  20. Petersen O. H. The effect of glucagon on the liver cell membrane potential. J Physiol. 1974 Jun;239(3):647–656. doi: 10.1113/jphysiol.1974.sp010587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pressman B. C., Harris E. J., Jagger W. S., Johnson J. H. Antibiotic-mediated transport of alkali ions across lipid barriers. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1949–1956. doi: 10.1073/pnas.58.5.1949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Scharschmidt B. F., Van Dyke R. W., Stephens J. E. Chloride transport by intact rat liver and cultured rat hepatocytes. Am J Physiol. 1982 Jun;242(6):G628–G633. doi: 10.1152/ajpgi.1982.242.6.G628. [DOI] [PubMed] [Google Scholar]
  23. Shotwell M. A., Kilberg M. S., Oxender D. L. The regulation of neutral amino acid transport in mammalian cells. Biochim Biophys Acta. 1983 May 24;737(2):267–284. doi: 10.1016/0304-4157(83)90003-5. [DOI] [PubMed] [Google Scholar]
  24. Sips H. J., Groen A. K., Tager J. M. Plasma-membrane transport of alanine is rate-limiting for its metabolism in rat-liver parenchymal cells. FEBS Lett. 1980 Oct 6;119(2):271–274. doi: 10.1016/0014-5793(80)80269-9. [DOI] [PubMed] [Google Scholar]
  25. Sips H. J., Van Amelsvoort J. M., Van Dam K. Amino acid transport in plasma-membrane vesicles from rat liver. Characterization of L-alanine transport. Eur J Biochem. 1980 Apr;105(2):217–224. doi: 10.1111/j.1432-1033.1980.tb04492.x. [DOI] [PubMed] [Google Scholar]
  26. Wondergem R., Harder D. R. Transmembrane potential and amino acid transport in rat hepatocytes in primary monolayer culture. J Cell Physiol. 1980 Jul;104(1):53–60. doi: 10.1002/jcp.1041040109. [DOI] [PubMed] [Google Scholar]

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