Neurochemical Research

, Volume 13, Issue 2, pp 105–111 | Cite as

Tricyclic antidepressants, mianserin, and ouabain stimulate inositol phosphate formation in vitro in rat cortical slices

  • Neville N. Osborne
Original Articles

Abstract

The ability of tricyclic antidepressants, monoamine oxidase inhibitors, mianserin and ouabain to stimulate hydrolysis of inositol phosphates was examined in rat cerebral cortex slices using a direct assay which involves labelling with [3H]inositol and assaying [3H]inositol phosphates in the presence of lithium. Desimipramine, imipramine, chlorimipramine, mianserin, and ouabain stimulated [3H]inositol phosphate accumulation in a concentration-dependent manner. The monoamine oxidase inhibitors, pargyline and nialamide were without effect. The stimulation of [3H]inositol phosphate accumulation caused by the various substances was not blocked by the antagonists prazosin, ketanserin, atropine, or mepyramine. In contrast, the antagonists prazosin, ketanserin, atropine and mepyramine selectively blocked stimulation of [3H]inositol phosphate accumulation caused by noradrenaline, serotonin, carbachol and histamine respectively. When desimipramine was substituted for lithium in the assay procedure, carbachol was ineffectual in stimulating [3H]inositol phosphate accumulation. In these experiments the control (unstimulated) values were much higher than in the normal (when lithium is present) assay procedure. Desimipramine is quite effective in stimulating [3H]inositol phosphate accumulation either in the presence or absence of lithium in the incubation medium. This is not the case for carbachol where it was essential to have lithium in the incubation medium in order to obtain a stimulation of [3H]inositol phosphate accumulation. Furthermore, in the case of carbachol stimulation, most of the radioactivity was associated with a peak corresponding to inositol monophosphate, while for desimipramine stimulation two clear peaks corresponding to inositol monophosphate and inositol bisphosphate were apparent.

Key Words

Inositol phosphate tricyclic antidepressants mianserin 

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References

  1. 1.
    Post, R. M., and Ballenger, J. C. 1984. Frontiers of Clinical Neuroscience, Vol. 1, Williams and Wilkins, Baltimore/London.Google Scholar
  2. 2.
    Costa, E., Revizza, L., and Barbaccia, M. L. 1986. Evaluation of Current Theories on the mode of action of antide-pressants. Pages 9–21,in G. Bartholini, K. G. Lloyd, and P. L. Morselli (eds.), GABA and Mood Disorders, L.E.R.S., Monograph Series, Raven Press, New York.Google Scholar
  3. 3.
    Horwell, D. C. 1985. Antidepressants. Pages 71–122,in D. R. Horwell (ed), Drugs in central nervous system disorders, Marcel Dekker, Inc., New York.Google Scholar
  4. 4.
    Hokin, M. R., and Hokin, L. E. 1953. Enzyme Secretion and the incorporation of phosphorous 32 into phospholipids of pancreas slices. J. Biol. Chem. 203:967–977.PubMedGoogle Scholar
  5. 5.
    Larrabee, M. G. 1968. Transsynaptic stimulation of phosphatidyl-inositol metabolism in sympathetic neurones in situ. J. Neurochem. 15:803–808.Google Scholar
  6. 6.
    Nahorski, S. R. 1985. Inositol phospholipid hydrolysis as a primary response to receptors not linked to adenylate cyclase. Arzneim-Forsch/Drug Res. 35:1886–1890.Google Scholar
  7. 7.
    Downes, C. P. 1986. Agonist-stimulated phosphatidylinositol 4,5-bisphosphate metabolism in the nervous system. Neurochem. Int. 9:211–230.Google Scholar
  8. 8.
    Michell, R. H. 1981. Phosphatidylinositol metabolism in signal transduction. Neuroscience Res. Prog. Bull. 20:339–350.Google Scholar
  9. 9.
    Berridge, M. J. 1986. Cell Signalling through phospholipid metabolism. J. Cell. Sci. Suppl. 4:137–153.Google Scholar
  10. 10.
    Berridge, M. J., and Irvine, R. F. 1984. Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321.PubMedGoogle Scholar
  11. 11.
    Nishizaka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308:693–697.PubMedGoogle Scholar
  12. 12.
    Berridge, M. J., Downes, C. P., and Hanley, M. R. 1982. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem. J. 206:587–595.PubMedGoogle Scholar
  13. 13.
    Brown, E., Kendall, D. A., and Nahorski, S. R. 1984. Inositol phospholipid hydrolysis in rat cerebral cortex slices I Receptor characterisation. J. Neurochem. 42:1379–1387.PubMedGoogle Scholar
  14. 14.
    Sherman, W. R., Munsell, L. Y., Gish, B. G., and Honchar, M. P. 1985. Effects of systemically administered lithium on phosphoinositide metabolism in rat brain, kidney and testis. J. Neurochem. 44:798–807.PubMedGoogle Scholar
  15. 15.
    Berridge, M. J., Dawson, R. M., Downes, C. P., Heslop, J. P., and Irvine, P. F. 1983. Changes in the levels of inositol phosphates after agonist-dependant hydrolysis of membrane phosphoinositides. Biochem. 212:473–482.PubMedGoogle Scholar
  16. 16.
    Batty, I. R., Nahrski, S. R., and Irvine, R. F. 1985. Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic stimulation of rat cortical slices. Biochem. J. 232:211–215.Google Scholar
  17. 17.
    Gonzales, R. A., and Crews, F. T. 1984. Characterization of the cholinergic stimulation of phosphoinisotide hydrolysis in rat brain slices. J. Neuroscience 4:3120–3127.Google Scholar
  18. 18.
    Conn, P. J., and Sanders-Bush, E. 1985. Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rate cerebral cortex but not in subcortical regions. J. Pharmacol. Expt. Therap. 234:195–203.Google Scholar
  19. 19.
    Kendall, D. A., and Nahorski, S. R. 1985. 5-Hydroxytryptamine-stimulated inositol phospholipid hydrolysis in rat cerebral cortex slices: pharmacological characterization and effects of antidepressants. J. Pharmacol. Expt. Therap. 223:473–479.Google Scholar
  20. 20.
    Simmons, D. A., Kern, E. F. O., Winegrad, A. I., and Martin, D. B. 1986. Basal phosphotidylinositol turnover controls aortic Na+/K+ ATPase activity Am. Soc. Clinical Investig. 77:503–513.Google Scholar
  21. 21.
    Leli, U., Froimowitz, M., and Hauser, G. 1986. Effects of cationic amphiphitic drugs and serotonin on phosphoinositide and inositol phosphate metabolism in C6 Glioma cells Page 271,in S. Tuček, S. Štipek, F. Štastny and J. Křivanek (eds.), Molecular basis of Neurol. Function E.S.N. abstracts.Google Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • Neville N. Osborne
    • 1
  1. 1.Nuffield Laboratory of OphthalmologyUniversity of OxfordOXFORDU.K.

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