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Effect of atropine and gammahydroxybutyrate on inschemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo

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Abstract

Brain ischemia in gerbils was induced by ligation of both common carotid arteries for 1 min or 10 min. Sham-operated animals served as controls. Intracerebral injection of [3H]inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between inositol lipids and water-soluble inositol phosphate.

A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of inositol triphosphate (IP3) and inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of phosphatase activation by the ischemic insult.

The agonist of the cholinergic receptor, carbachol, injected intracerebrally (40 μg per animal) increased accumulation of radioactivity in all inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively.

The muscarinic cholinergic antagonist, atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble inositol metabolites in the brain of animals pretreated with atropine was evidently about 32% lower than in untreated animals.

Pretreatment with atropine decreased the radioactivity of all inositol phosphates in the brain of animals subjected to 1-min ischemia and the radioactivity of IP in the case of 10-min brain ischemia. Gammabutyrolactone (GBL) administered intraperitoneally in the anesthetic dose 300 mg/kg body wt. diminished inositol monophosphate accumulation induced by either ischemic condition.

Results from these in vivo studies are evidence that the blockage of cholinergic receptors by atropine depresses the response of phosphoinositides to physiological and particularly pathological stimuli.

The results suggest that stimulation of the cholinergic receptor system is involved in the degradation of polyphosphoinositides during ischemia.

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References

  1. Strosznajder, J., Wikieł, H., and Sun, G. Y. 1985. Effect of ischemia on inositol metabolites in the gerbil brain. J. Neurochem. (Abstr.) 44 (suppl.) S25A.

    Google Scholar 

  2. Strosznajder, J., Wikieł, H., and Sun, G. Y. 1987. Effect of cerebral ischemia on polyphosphoinositide metabolism in gerbil brain subcellular fractions. J. Neurochem. 48:943–948.

    Google Scholar 

  3. Sekar, M. Ch., and Hokin, L. E. 1986. The role of phosphoinositides in signal transduction. J. Membrane Biol. 89:193–210.

    Google Scholar 

  4. Abdel-Latif, A. A. 1986. Calcium-mobilizing receptors polyphosphoinositides and the generation of second messengers. Pharmacol. Rev. 38:227–272.

    Google Scholar 

  5. Nishizuka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308:693–697.

    Google Scholar 

  6. Berridge, M. J. 1984. Inositol triphosphate and diacylglycerol as second messengers (Review article) Biochem. J. 220:345–360.

    Google Scholar 

  7. Nahorski, S. R., Kendall, D. A., and Batty, I. 1986. Receptor and phosphoinositide metabolism in the central nervous system. Biochem. Pharmacol. 35:2447–2453.

    Google Scholar 

  8. Bell, R. L., Kennerly, D. A., Stanford, N., and Malfus, P. W. 1979. Digliceride lipase A: A pathway for arachidonate release from human platelets. Proc. Natl. Acad. Sci. USA 76:3238–3241.

    Google Scholar 

  9. Kennerly, D. A., Sullivan, T. J., and Parker, C. W. 1979. Activation of phospholipid metabolism during mediator release from stimulated rat mast cells. J. Immunol. 122:152–157.

    Google Scholar 

  10. Rittenhouse-Simmons, S. 1979. Production of diglyceride from phosphatidylinositol in activated human platelets. J. Clin. Invest. 63:380–387.

    Google Scholar 

  11. Ehlerrt, F. J., Roeske, W. R., and Yamamura, H. I. 1981. Muscarinic receptor: regulation by guanine nucleotides ions and N-ethylmaleimide. Fed. Proc. 40:153–159.

    Google Scholar 

  12. Ehlert, F. J., Itoga, E., Roeske, W. R., and Yamamura, H. I. 1982. The interaction of 3H nitronolipine with receptors for calcium antagonist in the cerebral cortex and heart of rats. Biochim. Biophys. Res. Commun. 11, 104:937–943.

    Google Scholar 

  13. Caulfield, M. P., Higgins, G. A., and Straughan, D. W. 1983. Central administration of the muscarinic receptor subtypeselective antagonist pirezepine selectively impairs passive avoidance learning in the mouse. J. Pharm. Pharmacol. 35:131–132.

    Google Scholar 

  14. Wikieł, H., and Strosznajder, J. 1986. Effect of cholinergic agonist on polyphosphoinositides metabolism in normoxic and ischemic gerbil in vivo. In: Molecular basis of neural function (Tucek, S., Stipek, S., Stastny, F., and Krivanek, J., eds.). Abstracts of the Sixth ESN General Meeting in Prague, p. 337.

  15. Domanska-Janik, K., Lazarewicz, J. W., Noremberg, K., Strosznajder, J., and Zalewska, T., 1985. Effect of brain energy imbalance on phospholipids and neurotransmitter metabolism in synaptosomes. Neurochem. Res. 10:573–589.

    Google Scholar 

  16. Folch, J., Lees, M., and Sloane-Stanley, G. H. 1957. A single method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226:497–509.

    Google Scholar 

  17. Berridge, M. J., Dawson, R. M. C., Downes, C. P., Heslop, J. P., and Irvine, R. F. 1983. Changes in the levels of inositol phosphates after agonist dependent hydrolysis of membrane phosphoinositides. Biochem. J. 212:473–482.

    Google Scholar 

  18. Nemoto, E. M. 1984. Brain ischemia. In: Handbook of Neurochemistry (Lajtha, A. ed.) pp. 533–588, vol. 9, Plenum Press, New York.

    Google Scholar 

  19. Berridge, M. J. 1981. Phosphatidylinositol hydrolysis: a multifunctional transducing mechanism. Mol. Cell Endocrinol. 24:115–140.

    Google Scholar 

  20. Berridge, M. J. 1983. Rapid accumulation of inositol triphosphate reveals that agonist hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem. J. 212:849–858.

    Google Scholar 

  21. Michell, R. H., and Kirk, C. J. 1981. Why is phosphatidylinositol degraded in response to stimulation of certain receptors. Trends Pharmacol. Sci. 2:86–89.

    Google Scholar 

  22. Martin, T. F. 1983. Thyrotropin-releasing hormone rapidly activates the phosphodiester hydrolysis of polyphosphoinositides in GH3 pituitary cells. Evidence for the role of a polyphosphoinositide specific phospholipase C in hormone action. J. Biol. Chem. 258:14816–14822.

    Google Scholar 

  23. Downes, C. P., and Wusteman, M. M. 1983. Breakdown of polyphosphoinositides and not phosphatidylinositol account for muscarinic agonist—stimulated inositol phospholipid metabolism in rat parotid glands. Biochem. J. 216: 633–640.

    Google Scholar 

  24. Abdel-Latif, A. A., Smith, J. P., and Akhtar, R. A. 1985. Polyphosphoinositides and muscarinic cholinergic and α1 receptor, in the iris muscle. Pages 275–298in Bleasdale, J. E., Eichberg, J., and Hauser, G. (eds.), Inositol and phosphoinositides. Metabolism and Regulation. The Humana Press.

  25. Fisher, S. K. 1986. Inositol lipids and signal transduction at cns muscarinic receptors. In: Subtypes of Muscarinic Receptors II: Proceedings of the Second Intern. Symposium, 22–24 August 1985, Boston Massachusetts. Trends Pharmacol. Sci., suppl. Febr. 61–65.

  26. Baker, L. A., Dowdall, M. H., Essman, W. B., and Whittaker, V. P. 1970. The compartmentation of acetylcholine in cholinergic nerve terminals. Pagesin Heilbronn, E., and Winter, A. (eds.). Drugs and Cholinergic Mechanisms in the CNS. Stockholm, Forsvarets Forskningsanstalt.

    Google Scholar 

  27. Carola, E., and Costa, E. 1986. Potassium ion facilitation of phosphoinositide turnover activation by muscarinic receptor agonists in rat brain. J. Neurochem. 46:1429–1435.

    Google Scholar 

  28. Sethy, V. H., Roth, R. H., Walters, R. J., Marini, J., and Van Woert, M. H. 1976. Effect of anesthetic doses of hydroxybutyrate on the acetylcholine content of rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 295:9–14.

    Google Scholar 

  29. Sethy, V. H., Roth, R. H., Kuhar, M. J., and Van Woert, M. H. 1973. Choline and acetylcholine: Regional distribution and effect of degradation of cholinergic nerve terminals in the rat hippocampus. Neuropharmacology 12:819–823.

    Google Scholar 

  30. Sethy, V. H., Kuhar, M. J., Roth, R. H. Van Woert, M. H., and Aghajanian, G. K. 1973. Cholinergic neurons: effect of acute septal lesion on acetylcholine and choline content of rat hippocampus. Brain Res. 55:481–484.

    Google Scholar 

  31. Potempska, A., Gradkowska, M., and Oderfeld-Nowak, B. 1975. Early changes in acetylcholine pools in the hippocampus of rat brain after septal lesions. J. Neurochem. 24:787–789.

    Google Scholar 

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Author notes

  1. G. Halat (Visiting Scientist)

    Present address: Institute of Neurobiology, Centre of Physiological Sciences, Slovak Academy of Sciences, Kosice, Czechoslovakia

Authors and Affiliations

  1. Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 3 Dworkowa Str., 00-784, Warsaw, Poland

    H. Wikieł, G. Halat (Visiting Scientist) & J. Strosznajder

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Wikieł, H., Halat, G. & Strosznajder, J. Effect of atropine and gammahydroxybutyrate on inschemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo. Neurochem Res 13, 443–448 (1988). https://doi.org/10.1007/BF01268879

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