Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1989 Mar 1;258(2):621–624. doi: 10.1042/bj2580621

Potentiation by lithium of CMP-phosphatidate formation in carbachol-stimulated rat cerebral-cortical slices and its reversal by myo-inositol.

P P Godfrey 1
PMCID: PMC1138408  PMID: 2706006

Abstract

This paper describes a rapid and simple method for measuring CMP-phosphatidate (CMP-PA; CDP-diacylglycerol), providing a novel assay for inositol phospholipid metabolism. Rat cerebral-cortical slices labelled with [14C]cytidine were incubated with the muscarinic cholinergic agonist carbachol in the presence of various concentrations of LiCl; 10 mM-LiCl greatly enhanced the carbachol-stimulated formation of [14C]CMP-PA over a 60 min incubation period. The potentiation by Li+ was concentration-dependent, with a maximal enhancement at 3 mM and half-maximal enhancement at 0.6 mM-LiCl. The enhancement by Li+ could be reversed by incubation with myo-inositol; a maximal effect was observed with 10 mM-inositol. A similar, though smaller, enhancement of CMP-PA concentrations in the presence of LiCl was observed in slices stimulated with noradrenaline, 5-hydroxytryptamine and K+. The results are discussed in relation to previously observed effects of Li+ on inositol phospholipid metabolism.

Full text

PDF

Selected References

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

  1. AGRANOFF B. W., BRADLEY R. M., BRADY R. O. The enzymatic synthesis of inositol phosphatide. J Biol Chem. 1958 Nov;233(5):1077–1083. [PubMed] [Google Scholar]
  2. Allison J. H., Blisner M. E., Holland W. H., Hipps P. P., Sherman W. R. Increased brain myo-inositol 1-phosphate in lithium-treated rats. Biochem Biophys Res Commun. 1976 Jul 26;71(2):664–670. doi: 10.1016/0006-291x(76)90839-1. [DOI] [PubMed] [Google Scholar]
  3. Allison J. H., Stewart M. A. Reduced brain inositol in lithium-treated rats. Nat New Biol. 1971 Oct 27;233(43):267–268. doi: 10.1038/newbio233267a0. [DOI] [PubMed] [Google Scholar]
  4. Angchanpen P., Marin-Grez M., Schnermann J. Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline. Br J Pharmacol. 1988 Jan;93(1):151–155. doi: 10.1111/j.1476-5381.1988.tb11416.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Batty I., Nahorski S. R. Lithium inhibits muscarinic-receptor-stimulated inositol tetrakisphosphate accumulation in rat cerebral cortex. Biochem J. 1987 Nov 1;247(3):797–800. doi: 10.1042/bj2470797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berridge M. J., Downes C. P., Hanley M. R. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982 Sep 15;206(3):587–595. doi: 10.1042/bj2060587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  8. Burgess G. M., McKinney J. S., Irvine R. F., Putney J. W., Jr Inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate formation in Ca2+-mobilizing-hormone-activated cells. Biochem J. 1985 Nov 15;232(1):237–243. doi: 10.1042/bj2320237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Downes C. P., Stone M. A. Lithium-induced reduction in intracellular inositol supply in cholinergically stimulated parotid gland. Biochem J. 1986 Feb 15;234(1):199–204. doi: 10.1042/bj2340199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fisher S. K., Agranoff B. W. Receptor activation and inositol lipid hydrolysis in neural tissues. J Neurochem. 1987 Apr;48(4):999–1017. doi: 10.1111/j.1471-4159.1987.tb05618.x. [DOI] [PubMed] [Google Scholar]
  11. Ghalayini A., Eichberg J. Purification of phosphatidylinositol synthetase from rat brain by CDP-diacylglycerol affinity chromatography and properties of the purified enzyme. J Neurochem. 1985 Jan;44(1):175–182. doi: 10.1111/j.1471-4159.1985.tb07128.x. [DOI] [PubMed] [Google Scholar]
  12. Gibson A., Brammer M. J. The influence of divalent cations and substrate concentration on the incorporation of myo-inositol into phospholipids of isolated bovine oligodendrocytes. J Neurochem. 1981 Mar;36(3):868–874. doi: 10.1111/j.1471-4159.1981.tb01674.x. [DOI] [PubMed] [Google Scholar]
  13. Godfrey P. P., Putney J. W., Jr Receptor-mediated metabolism of the phosphoinositides and phosphatidic acid in rat lacrimal acinar cells. Biochem J. 1984 Feb 15;218(1):187–195. doi: 10.1042/bj2180187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Godfrey P. P., Wilkins C. J., Tyler W., Watson S. P. Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rat cerebral cortex. Br J Pharmacol. 1988 Sep;95(1):131–138. doi: 10.1111/j.1476-5381.1988.tb16556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hallcher L. M., Sherman W. R. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980 Nov 25;255(22):10896–10901. [PubMed] [Google Scholar]
  16. Hughes P. J., Drummond A. H. Formation of inositol phosphate isomers in GH3 pituitary tumour cells stimulated with thyrotropin-releasing hormone. Acute effects of lithium ions. Biochem J. 1987 Dec 1;248(2):463–470. doi: 10.1042/bj2480463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kendall D. A., Nahorski S. R. Acute and chronic lithium treatments influence agonist and depolarization-stimulated inositol phospholipid hydrolysis in rat cerebral cortex. J Pharmacol Exp Ther. 1987 Jun;241(3):1023–1027. [PubMed] [Google Scholar]
  18. Majerus P. W., Connolly T. M., Bansal V. S., Inhorn R. C., Ross T. S., Lips D. L. Inositol phosphates: synthesis and degradation. J Biol Chem. 1988 Mar 5;263(7):3051–3054. [PubMed] [Google Scholar]
  19. Mantelli L., Capanni L., Corti V., Bennardini F., Matucci R., Ledda F. Influence of lithium on the positive inotropic effect of phenylephrine and isoprenaline in guinea-pig heart. Eur J Pharmacol. 1988 May 20;150(1-2):123–129. doi: 10.1016/0014-2999(88)90757-1. [DOI] [PubMed] [Google Scholar]
  20. Mustelin T., Pösö H., Iivanainen A., Andersson L. C. myo-Inositol reverses Li+-induced inhibition of phosphoinositide turnover and ornithine decarboxylase induction during early lymphocyte activation. Eur J Immunol. 1986 Jul;16(7):859–861. doi: 10.1002/eji.1830160724. [DOI] [PubMed] [Google Scholar]
  21. Sherman W. R., Gish B. G., Honchar M. P., Munsell L. Y. Effects of lithium on phosphoinositide metabolism in vivo. Fed Proc. 1986 Oct;45(11):2639–2646. [PubMed] [Google Scholar]
  22. Spector R., Lorenzo A. V. Myo-inositol transport in the central nervous system. Am J Physiol. 1975 May;228(5):1510–1518. doi: 10.1152/ajplegacy.1975.228.5.1510. [DOI] [PubMed] [Google Scholar]
  23. Takenawa T., Egawa K. CDP-diglyceride:inositol transferase from rat liver. Purification and properties. J Biol Chem. 1977 Aug 10;252(15):5419–5423. [PubMed] [Google Scholar]
  24. Watson S. P., Godfrey P. P. The role of receptor-stimulated inositol phospholipid hydrolysis in the autonomic nervous system. Pharmacol Ther. 1988;38(3):387–417. doi: 10.1016/0163-7258(88)90011-3. [DOI] [PubMed] [Google Scholar]
  25. Whitworth P., Kendall D. A. Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices. J Neurochem. 1988 Jul;51(1):258–265. doi: 10.1111/j.1471-4159.1988.tb04865.x. [DOI] [PubMed] [Google Scholar]
  26. Worley P. F., Heller W. A., Snyder S. H., Baraban J. M. Lithium blocks a phosphoinositide-mediated cholinergic response in hippocampal slices. Science. 1988 Mar 18;239(4846):1428–1429. doi: 10.1126/science.2831626. [DOI] [PubMed] [Google Scholar]

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

RESOURCES