Skip to main content
Log in

Time-course of malaoxon-induced alterations in brain regional inositol-1-phosphate levels in convulsing and nonconvulsing rats

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The potential of a single dose of malaoxon (26.2 or 39.2 mg/kg i.p.) to produce convulsions and to increase cerebral levels of inositol-1-phosphate (Ins1P), an intermediate in phosphoinositide (PI) cycle, was followed for 1, 4, or 72 hr. The lower dose of malaoxon did not produce convulsions whereas the higher dose induced convulsions in 60% of the exposed rats. Malaoxon caused a dosedependent, at most 2-fold, increase in brain regional Ins1P levels in nonconvulsing rats as compared to controls. At the higher dose of malaoxon, in convulsing rats, the Ins1P-levels increased 4-fold above the control Ins1P-levels. In nonconvulsing rats, the Ins1P-levels reached their maximum 1–4 hr after the administration of malaoxon, whereas in convulsing rats the levels increased for 72 hr. The results suggest that PI-signalling is associated with convulsions produced by malaoxon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Meldrum, B. S. 1986. Cell damage in epilepsy and the role of calcium in cytotoxicity. Adv. Neurol. 44:849–855.

    PubMed  Google Scholar 

  2. Olney, J. W., Collins R. C., and Sloviter R. S. 1986. Excitotoxic mechanism of epileptic brain damage. Adv. Neurol. 44:857–878.

    PubMed  Google Scholar 

  3. Collins, R. C., Lothman E. W., and Olney J. W. 1983. Status epilepticus in the limbic system: Biochemical and pathological changes. Adv. Neurol 34:277–288.

    PubMed  Google Scholar 

  4. Pazdernik, T. L., Cross, R. S., Giesler, M., Samson F. E., and Nelson, R. S. 1985. Changes in local cerebral glucose utilization induced by convulsants. Neuroscience 14:823–835.

    PubMed  Google Scholar 

  5. Flynn, C. J., and Wecker, L. 1986. Elevated choline levels in brain: A noncholinergic component of organophosphate toxicity. Biochem. Pharmacol. 35:3115–3121.

    PubMed  Google Scholar 

  6. Gonchar, M. P., Olney, J. W., and Sherman, W. R. 1983. Systemic cholinergic agents induced seizures and brain damage in lithium-treated rats. Science 220:323–325.

    PubMed  Google Scholar 

  7. Gonzales, R. A., and Crews, F. T. 1985. Cholinergic- and adrenergic-stimulated inositide hydrolysis in brain: Interaction, regional distribution, and coupling mechanisms. J. Neurochem. 45:1076–1084.

    PubMed  Google Scholar 

  8. Savolainen, K. M., Terry, J. B., Nelson, S. R., Samson F. E., and Pazdernik, T. L. 1988. Convulsions and cerebral inositol-1-phosphate levels in rats treated with diisopropyl fluorophosphate. Pharmacol & Toxicol 63:137–138.

    Google Scholar 

  9. Rooney, T. A., Nahorski, S. R. 1986. Regional characterization of agonist and depolarization-induced phosphoinositide hydrolysis in rat brain. J. Pharmacol. Exp. Ther. 239:873–880.

    PubMed  Google Scholar 

  10. Fisher, S. K., and Agranoff, B. W. 1986. Receptor activation and inositol lipid hydrolysis in neural tissues. J. Neurochem. 48:999–1017.

    Google Scholar 

  11. Berridge, M. J., and Irvine, R. F. 1984. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature (London) 312:315–321.

    Google Scholar 

  12. Berridge, M.J. 1986. Inositol phosphates as second messengers. Pages 25–45in Putney, J. W. (ed.), Phosphoinositides and receptor mechanisms, Alan R. Liss, Inc., New York.

    Google Scholar 

  13. Irvine, R. F. 1986. The structure, metabolism, and analysis of inositol phosphates. Pages 89–107,in Putney, J. W. (ed.), Phosphoinositides and receptor mechanisms, Alan R. Liss., Inc., New York.

    Google Scholar 

  14. Berridge, M. J., Downes, C. P., and Hanley, M. R. 1982. Lithium amplifies agonist-dependent phosphatidyl-inositol responses in brain and salivary glands. Biochem. J. 206:587–598.

    PubMed  Google Scholar 

  15. Sherman, W. R., Gish, B. G., Honchar, M. P., and Munsell, L. Y. 1986. Effects of lithium on phosphoinositide metabolism in vivo. Fed. Proc. 45:2639–2646.

    PubMed  Google Scholar 

  16. Pellegrino, L. J., Pellegrino, A. S., and Gushman, A. J. 1979. A Stereotaxic atlas of the rat brain, 2nd ed., Plenum Press, New York.

    Google Scholar 

  17. Hirvonen, M.-R., Lihtamo, H., Savolainen, K. 1988. A gas chromatographic method for the determination of inositol monophosphates in rat brain. Neurochemical Research (in press).

  18. Hirasawa, K., and Nishizuka, Y. 1985. Phosphatidylinositol turnover in receptor mechanism and signal transduction. Ann. Rev. Pharmacol. Toxicol. 25:147–170.

    Google Scholar 

  19. Kikkawa, U., and Nishizuka, Y. 1987. Inositol phospholipid turnover and protein kinase C in stimulus-response coupling. Biochem. Soc. Transact. 15:124–125.

    Google Scholar 

  20. Hallcher, L. M., and Sherman, W. R. 1980. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J. Biol. Chem. 225:10896–10901.

    Google Scholar 

  21. Olney, J. W., deGubareff, T., and Labruyere, J. 1983. Seizurerelated brain damage induced by cholinergic agents. Nature (London) 301:520–522.

    Google Scholar 

  22. Piredda, S., Lim C. R., and Gale, K. 1985. Intracerebral site of convulsant action of biculline. Life Sci. 36, 1295–1298.

    PubMed  Google Scholar 

  23. Piredda, S., and Gale, K. 1986. Role of excitatory amino acid transmission in the genesis of seizures elicited from the deep prepiriform cortex. Brain Res. 377:205–210.

    PubMed  Google Scholar 

  24. Browning, R. A. 1986. Neuroanatomical localization of structures responsible for seizures in the GEPR: Lesion studies. Life Sci. 39:857–867.

    PubMed  Google Scholar 

  25. Kuhar, M. I., and Yamamura, I.H. 1975. Light autoradiographic localization of cholinergic muscarinic receptors in rat brain by specific binding of a potent antagonist. Nature (London) 253:560–561.

    Google Scholar 

  26. Churchill, L., Pazdernik, T. L., Samson, F., and Nelson, S. R. 1984. Topographical distribution of down-regulated muscarinic receptors in rat brains after repeated exposure to diisopropyl phosphofluoridate. Neuroscience 11:463–472.

    PubMed  Google Scholar 

  27. Jope, R. S., Simonato, M., and Lally, K. 1987. Acetylcholine content in rat brain is elevated by status epilepticus induced by lithium and pilocarpine. J. Neurochem. 49:944–951.

    PubMed  Google Scholar 

  28. Shih, T.-M., 1982. Time course effects of soman on acetylcholine levels in six discrete areas of the rat brain. Psychopharmacology 78:170–175.

    PubMed  Google Scholar 

  29. Fonnum, F., and Guttormsen, D. M. 1969. Changes in acetylcholine content of rat brain after toxic doses of di-isopropyl phosphorofluoridate, Experientia 25:505–506.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirvonen, MR., Komulainen, H., Paljärvi, L. et al. Time-course of malaoxon-induced alterations in brain regional inositol-1-phosphate levels in convulsing and nonconvulsing rats. Neurochem Res 14, 143–147 (1989). https://doi.org/10.1007/BF00969629

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00969629

Key Words

Navigation