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. 1986 Feb 15;234(1):199–204. doi: 10.1042/bj2340199

Lithium-induced reduction in intracellular inositol supply in cholinergically stimulated parotid gland.

C P Downes, M A Stone
PMCID: PMC1146545  PMID: 3707540

Abstract

The effects of lithium and cholinergic stimulation on inositol phospholipid metabolism have been assessed using rat parotid gland slices and isolated acinar cells labelled with 32Pi. Cholinergic stimulation using carbachol caused substantial breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and enhanced labelling of phosphatidate (PA) and phosphatidylinositol (PtdIns). Lithium alone had little effect upon 32Pi incorporation, but in combination with carbachol it greatly reduced the PtdIns labelling response to the agonist. Instead the label accumulated in a lipid identified as cytidine monophosphorylphosphatidate. There was also an enhancement of the PA labelling response to carbachol. These lithium-induced alterations in agonist-stimulated phospholipid metabolism were reversed if 10-30 mM-inositol was included in the incubation medium. Despite reduced PtdIns synthesis, lithium had relatively little effect on polyphosphoinositide labelling in stimulated cells. Resynthesis of polyphosphoinositides was monitored in acinar cells that had been stimulated with carbachol and then treated with atropine to block muscarinic receptors. Treatment with lithium during the carbachol-stimulation phase reduced the rate of phosphatidylinositol 4-phosphate synthesis, but had no significant effect upon PtdInsP2. The results suggest that an active inositol phosphatase pathway is essential to maintain intracellular inositol levels, but that PtdInsP2 synthesis is not markedly reduced by a substantial fall in intracellular inositol. This implies a close control over the rates of PtdInsP2 breakdown and resynthesis during agonist stimulation.

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Selected References

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  1. 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]
  2. Aub D. L., Putney J. W., Jr Metabolism of inositol phosphates in parotid cells: implications for the pathway of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate. Life Sci. 1984 Apr 2;34(14):1347–1355. doi: 10.1016/0024-3205(84)90006-7. [DOI] [PubMed] [Google Scholar]
  3. Belmaker R. H., Lerer B., Klein E., Newman M., Dick E. Clinical implications of research on the mechanism of action of lithium. Prog Neuropsychopharmacol Biol Psychiatry. 1983;7(2-3):287–296. doi: 10.1016/0278-5846(83)90118-5. [DOI] [PubMed] [Google Scholar]
  4. Berridge M. J., Buchan P. B., Heslop J. P. Relationship of polyphosphoinositide metabolism to the hormonal activation of the inset salivary gland by 5-hydroxytryptamine. Mol Cell Endocrinol. 1984 Jun;36(1-2):37–42. doi: 10.1016/0303-7207(84)90082-0. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [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. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Downes C. P., Dibner M. D., Hanley M. R. Sympathetic denervation impairs agonist-stimulated phosphatidylinositol metabolism in rat parotid glands. Biochem J. 1983 Sep 15;214(3):865–870. doi: 10.1042/bj2140865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Downes C. P., Mussat M. C., Michell R. H. The inositol trisphosphate phosphomonoesterase of the human erythrocyte membrane. Biochem J. 1982 Apr 1;203(1):169–177. doi: 10.1042/bj2030169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Downes C. P., Wusteman M. M. Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands. Biochem J. 1983 Dec 15;216(3):633–640. doi: 10.1042/bj2160633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Downes P., Michell R. H. Phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate: lipids in search of a function. Cell Calcium. 1982 Oct;3(4-5):467–502. doi: 10.1016/0143-4160(82)90031-8. [DOI] [PubMed] [Google Scholar]
  13. Drummond A. H., Raeburn C. A. The interaction of lithium with thyrotropin-releasing hormone-stimulated lipid metabolism in GH3 pituitary tumour cells. Enhancement of stimulated 1,2-diacylglycerol formation. Biochem J. 1984 Nov 15;224(1):129–136. doi: 10.1042/bj2240129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. EGGMAN L. D., HOKIN L. E. The relationship between secretory activity and the incorporation of P32 into phosphoinositide and phosphotidic acid in salivary glands and pigeon esophageal mucosa in vitro. J Biol Chem. 1960 Sep;235:2569–2571. [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. Jacobson M. D., Wusteman M., Downes C. P. Muscarinic receptors and hydrolysis of inositol phospholipids in rat cerebral cortex and parotid gland. J Neurochem. 1985 Feb;44(2):465–472. doi: 10.1111/j.1471-4159.1985.tb05437.x. [DOI] [PubMed] [Google Scholar]
  17. Jolles J., Zwiers H., Dekker A., Wirtz K. W., Gispen W. H. Corticotropin-(1--24)-tetracosapeptide affects protein phosphorylation and polyphosphoinositide metabolism in rat brain. Biochem J. 1981 Jan 15;194(1):283–291. doi: 10.1042/bj1940283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones L. M., Michell R. H. Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments. Biochem J. 1974 Sep;142(3):583–590. doi: 10.1042/bj1420583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kanagasuntheram P., Randle P. J. Calcium metabolism and amylase release in rat parotid acinar cells. Biochem J. 1976 Dec 15;160(3):547–564. doi: 10.1042/bj1600547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  21. Prpić V., Blackmore P. F., Exton J. H. myo-Inositol uptake and metabolism in isolated rat liver cells. J Biol Chem. 1982 Oct 10;257(19):11315–11322. [PubMed] [Google Scholar]
  22. Putney J. W., Jr Biphasic modulation of potassium release in rat parotid gland by carbachol and phenylephrine. J Pharmacol Exp Ther. 1976 Aug;198(2):375–384. [PubMed] [Google Scholar]
  23. Putney J. W., Jr Inositol lipids and cell stimulation in mammalian salivary gland. Cell Calcium. 1982 Oct;3(4-5):369–383. doi: 10.1016/0143-4160(82)90024-0. [DOI] [PubMed] [Google Scholar]
  24. Putney J. W., Jr, McKinney J. S., Aub D. L., Leslie B. A. Phorbol ester-induced protein secretion in rat parotid gland. Relationship to the role of inositol lipid breakdown and protein kinase C activation in stimulus-secretion coupling. Mol Pharmacol. 1984 Sep;26(2):261–266. [PubMed] [Google Scholar]
  25. Seyfred M. A., Farrell L. E., Wells W. W. Characterization of D-myo-inositol 1,4,5-trisphosphate phosphatase in rat liver plasma membranes. J Biol Chem. 1984 Nov 10;259(21):13204–13208. [PubMed] [Google Scholar]
  26. Sherman W. R., Leavitt A. L., Honchar M. P., Hallcher L. M., Phillips B. E. Evidence that lithium alters phosphoinositide metabolism: chronic administration elevates primarily D-myo-inositol-1-phosphate in cerebral cortex of the rat. J Neurochem. 1981 Jun;36(6):1947–1951. doi: 10.1111/j.1471-4159.1981.tb10819.x. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Stanley P. E., Williams S. G. Use of the liquid scintillation spectrometer for determining adenosine triphosphate by the luciferase enzyme. Anal Biochem. 1969 Jun;29(3):381–392. doi: 10.1016/0003-2697(69)90323-6. [DOI] [PubMed] [Google Scholar]
  29. Storey D. J., Shears S. B., Kirk C. J., Michell R. H. Stepwise enzymatic dephosphorylation of inositol 1,4,5-trisphosphate to inositol in liver. Nature. 1984 Nov 22;312(5992):374–376. doi: 10.1038/312374a0. [DOI] [PubMed] [Google Scholar]
  30. Weiss S. J., McKinney J. S., Putney J. W., Jr Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells. Biochem J. 1982 Sep 15;206(3):555–560. doi: 10.1042/bj2060555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weiss S. J., McKinney J. S., Putney J. W., Jr Regulation of phosphatidate synthesis by secretagogues in parotid acinar cells. Biochem J. 1982 May 15;204(2):587–592. doi: 10.1042/bj2040587. [DOI] [PMC free article] [PubMed] [Google Scholar]

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