Effects of Lithium Ions on the Metabolism of Phosphoinositides

  • D. van Calker
  • W. Greil


The possibility that the therapeutic and prophylactic properties of lithium ions may be explained at least in part by their unique effects on the metabolism of phosphoinositides has attracted much attention. A decrease in the inositol content and a concomitant increase in the inositol-monophosphate concentration in the brain of lithium-treated animals was identified during the 1970s.1,2 However, only the elucidation of the pivotal role of phosphoinositide-derived second messenger molecules has allowed us to realize the significance of these findings (for reviews see refs. 3–6).


Lithium Salt Messenger Molecule Adenylate Cyclase System Prophylactic Property Inositol Content 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allison JH, Stewart MA. Reduced brain inositol in lithium-treated rats. Nature 1971; 233: 267 – 268.CrossRefGoogle Scholar
  2. 2.
    Allison JH, Blisner ME, Holland WH, et al. Increased brain myo-inositol 1-phosphate in lithium-treated rats. Biochem Biophys Res Commun 1976; 71: 664 – 670.PubMedCrossRefGoogle Scholar
  3. 3.
    Majerus PW, Conolly TM, Deckmyn H, et al. The metabolism of phosphoinositide-derived messenger molecules. Science 1986; 234: 1519 – 1526.PubMedCrossRefGoogle Scholar
  4. 4.
    Nahorski SR, Kendall DA, Batty I. Receptors and phosphoinositide metabolism in the central nervous system. Biochem Pharmacol 1986; 35: 2447 – 2453.PubMedCrossRefGoogle Scholar
  5. 5.
    Marx JL. Polyphosphoinositide research updated. Science 1987; 235: 974 – 976.PubMedCrossRefGoogle Scholar
  6. 6.
    Drummond AH. Lithium and inositol lipid-linked signalling mechanisms. Trends Pharm Sci 1987; 8: 129 – 133.CrossRefGoogle Scholar
  7. 7.
    Kaczmarek LK. The role of protein kinase C in the regulation of ion channels and neurotransmitter release. Trends Neurosci 1987; 10: 30 – 34.CrossRefGoogle Scholar
  8. 8.
    Irvine RF, Moor RM. Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J 1986; 240: 917 – 920.PubMedGoogle Scholar
  9. 9.
    Irvine RF, Letcher AJ, Lander DJ, et al. Specificity of inositol phosphate-stimulated Ca2+ mobilization from Swiss-mouse 3T3 cells. Biochem J 1986; 240: 301 – 304.PubMedGoogle Scholar
  10. 10.
    Hallcher LM, Sherman WR. The effect of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem 1980; 255: 10896 – 10901.PubMedGoogle Scholar
  11. 11.
    Van Calker D, Greil W. Effects of lithium ions on the metabolism of phosphoinositides: studies with rat pheochromocytoma cells (PC-12 cells). Pharmacopsychiatry 1986; 19: 276 – 277.CrossRefGoogle Scholar
  12. 12.
    Van Calker D, Assmann K, Greil W. Stimulation by bradykinin, angiotensin II and carbachol of the accumulation of inositolphosphates in PC-12 pheochromocytoma cells: differential effects of lithium ions on inositol mono- and polyphosphates. J Neurochem 1987; 49: 1379 – 1385.PubMedCrossRefGoogle Scholar
  13. 13.
    Burgess GM, McKinney JS, Irvine RF, et al. Inositol 1,4,5-triphosphate and inositol 1,3,4-triphosphate formation in Ca2+-mobilizing-hormone-activated cells. Biochem J 1985; 232: 237 – 243.PubMedGoogle Scholar
  14. 14.
    Hansen CA, Mah S, Williamson JR. Formation and metabolism of inositol 1,3,4,5-tetrakisphosphate in liver. J Biol Chem 1986; 261: 8100 – 8103.PubMedGoogle Scholar
  15. 15.
    Berridge MJ, Downes CP, Hanley MR. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 1982; 206: 587 – 595.PubMedGoogle Scholar
  16. 16.
    Drummond AH, Raeburn CA. The interaction of lithium with thyrotropin-releasing hormone-stimulated lipid metabolism in GH3 pituitary tumor cells. Biochem J 1984; 224: 129 – 136.PubMedGoogle Scholar
  17. 17.
    Downes CP, Stone MA. Lithium-induced reduction in intracellular inositol supply in cholinergically stimulated parotid gland. Biochem J 1986; 234: 199 – 204.PubMedGoogle Scholar
  18. 18.
    Ackermann KE, Gish BG, Honchar MP, et al. Evidence that inositol 1-phosphate in brain of lithium-treated rats results mainly from phosphatidylinositol metabolism. Biochem J 1987; 242: 517 – 524.PubMedGoogle Scholar
  19. 19.
    Van Calker D, Greil W. Biochemische und zellphysiologische Effekte von Lithiumionen. In: Müller-Oerlinghausen B, Greil W (eds): Die Lithiumtherapie. Berlin: Springer Press, 1986; 5 – 34.Google Scholar
  20. 20.
    Kikkawa U, Nishizuka Y. The role of protein kinase C in transmembrane signalling. Annu Rev Cell Biol 1986; 2: 149 – 178.PubMedCrossRefGoogle Scholar
  21. 21.
    Sibley DR, Lefkowitz RJ. Molecular mechanisms of receptor desensitization using the β-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 1985; 317: 124 – 129.PubMedCrossRefGoogle Scholar
  22. 22.
    Enna SJ, Karbon EW. Receptor regulation: evidence for a relationship between phospholipid metabolism and neurotransmitter receptor-mediated cAMP formation in brain. Trends Pharm Sci 1987; 8: 21 – 24.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1989

Authors and Affiliations

  • D. van Calker
  • W. Greil

There are no affiliations available

Personalised recommendations