Skip to main content
SpringerLink
Log in

Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The present studies examined the inhibitory effect of veratridine (a Na+ channel activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. Veratridine inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation (after a delay of about 30 seconds) at 60 or 120 seconds when there was little inhibition of inositol 1,4,5 trisphophate accumulation. The inhibitory effect of veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate accumulation was abolished in the presence of ouabain or tetrodotoxin but was unaffected in low calcium conditions. Veratridine reduced the total ATP content and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but not 30 μM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in the presence of carbachol was reversed by the presence of exogenous 8-bromo cyclic AMP or forskolin which activates adenylylcyclase. However, the decrease in brain slice ATP seen in the presence of veratridine was unaffected by forskolin. Our results are compatible with the hypothesis that veratridine inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5-P3.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Ins 1,4,5-P3 :

inositol 1,4,5 trisphosphate

Ins 1,3,4,5-P4 :

inositol 1,3,4,5-tetrakisphosphate

PMA:

phorbol 12-myristate 13-acetate

References

  1. Fisher, S. K., Heacock, A. M., and Agranoff, B. W. 1992. Inositol lipids and signal transduction in the nervous system: An update. J. Neurochem. 58:18–38.

    Google Scholar 

  2. Berridge, M., and Irvine, R. F. 1989. Inositol phosphates and cell signalling. Nature 341:197–205.

    Google Scholar 

  3. Challiss, R. A., and Nahorski, S. R. 1991. Depolarization and agonist-stimulated changes in inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate mass accumulation in rat cerebral cortex. J. Neurochem. 57:1042–1051.

    Google Scholar 

  4. Baird, J. G., and Nahorski, S. R. 1991. Stimulatory and inhibitory effects of N-methyl-D-aspartate on3H inositol polyphosphate accumulation in rat cortical slices. J. Neurochem. 57:629–635.

    Google Scholar 

  5. Myles, M. E., and Fain, J. N. 1994. Carbachol, but not norepinephrine, NMDA, ionomycin, ouabain, or phorbol myristate acetate, increases inositol 1,3,4,5-tetrakisphosphate accumulation in rat brain cortical slices. J. Neurochem. 62:2333–2339.

    Google Scholar 

  6. Batty, I. R., Nahorski, S. R., and Irvine, R. F. 1985. Rapid formation of inositol 1,3,4,5-tetrakisphosphate following muscarinic receptor stimulation of rat cerebral cortical slices. Biochem. J. 232:211–215.

    Google Scholar 

  7. Blaustein, M. P., and Goldring, J. M. 1975. Membrane potentials in pinched-off presynaptic nerve terminals monitored with a fluorescent probe: evidence that synaptosomes have potassium diffusion potentials. J. Physiol. 247:589–615.

    Google Scholar 

  8. Catterall, W. A. 1984. The molecular basis of neuronal excitability. Science 223:653–661.

    Google Scholar 

  9. Kendall, D. A., and Nahorski, S. R. 1984. Inositol phospholipid hydrolysis in rat cerebral cortical slices: II. Calcium requirement. J. Neurochem. 42:1388–1394.

    Google Scholar 

  10. Maier, K. U., and Rutledge, C. O. 1987. Comparison of norepinephrine- and veratrine-induced phosphoinositide hydrolysis in rat brain. J. Pharmacol. Exp. Ther. 240:729–736.

    Google Scholar 

  11. Lee, H.-M., and Fain, J. N. 1992. Magnesium dependent inhibition of agonist-stimulated phosphoinositide breakdown in rat cortical slices by excitatory amino acids. J. Neurochem. 59:953–962.

    Google Scholar 

  12. Chuang, D.-M. 1990. Regulation by batrachotoxin, veratridine, and monensin of basal and carbachol-induced phosphoinositide hydrolysis in neurohybrid NCB-20 cells. Neurochem. Res. 15: 695–704.

    Google Scholar 

  13. Donie, F., and Reiser, G. 1991. Mass measurements of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in a neuronal cell line stimulated with bradykinin: Inositol phosphate response shows desensitization. Biochem. Biophys. Res. Commun. 181:997–1003.

    Google Scholar 

  14. Fain, J. 1979. Effect of lipolytic agents on adenosine and AMP formation by fat cells. Biochim. Biophys. Acta. 573:510–520.

    Google Scholar 

  15. Salomon, Y., Londos, C., and Rodbell, M. 1974. A highly sensitive adenylate cyclase assay. Anal. Biochem. 58:541–548.

    Google Scholar 

  16. Baudry, M., Evans, J., and Lynch, G. 1986. Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonist in hippocampus. Nature 319:329–331.

    Google Scholar 

  17. Godfrey, P. P., Wilkins, C. J., Tyler, W., and Watson, S. P. 1988. Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rat cerebral cortex. Br. J. Pharmacol. 95:131–138.

    Google Scholar 

  18. Bjorndahl, J. M., and Rutledge, C. O. 1986. Effects of secretagogues on ATP levels and protein carboxyl methylation in rat brain synaptosomes. J. Pharmacol. Exp. Therap. 237:569–576.

    Google Scholar 

  19. Li, M., West, J. W., Lai, Y., Scheuer, T., and Catterall, W. A. 1992. Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1151–1159.

    Google Scholar 

  20. Li, M., West, J. W., Numann, R., Murphy, B. J., Scheuer, T., and Catterall, W. A. 1993. Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science 261:1439–1442.

    Google Scholar 

  21. Erneux, C., Moreau, C., Vandermeers, A., and Takazawa, K. 1993. Interaction of calmodulin with a putative calmodulin-binding domain of inositol 1,4,5-triphosphate 3-kinase (Effects of synthetic peptides and site-directed mutagenesis of Trp165). Eur. J. Biochem. 214:497–501.

    Google Scholar 

  22. Sim, S. S., Kim, J. W., and Rhee, S. G. 1990. Regulation of d-myo-inositol 1,4,5-trisphosphate 3-kinase by cAMP-dependent protein kinase and protein kinase. C. J. Biol. Chem. 265:10367–10372.

    Google Scholar 

  23. Ismail-Beigi, F., and Edelman, I. S. 1971. The mechanism of the calorigenic action of thyroid hormone. J. Gen. Physiol. 57:710–722.

    Google Scholar 

  24. Berrebi-Bertrand, I., Maixent, J.-M., Christie, G., and Lelievre, L. G. 1990. Two active Na+/K+-ATPases of high affinity for ouabain in adult rat brain membranes. Biochim. Biophys. Acta. 1021:148–156.

    Google Scholar 

  25. Go, M., Uchida, T., Takazawa, K., Endo, T., Erneux, C., Mailleux, P., and Onaya, T. 1993. Inositol 1,4,5-trisphosphate 3-kinase is found at highest levels in the dendritic spines of cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. Neurosci. Lett. 158:135–138.

    Google Scholar 

  26. Yamada, M., Kakita, A., Mizuguchi, M., Rhee, S. G., Kim, S. U., and Ikuta, F. 1993a. Specific expression of inositol 1,4,5-trisphosphate 3-kinase in dendritic spines. Brain Res. 606:335–340.

    Google Scholar 

  27. Yamada, M., Kakita, A., Mizuguchi, M., Rhee, S. G., Kim, S. U., and Ikuta, F. 1993b. Developmental profile of inositol 1,4,5-trisphosphate 3-kinase in rat cerebellar cortex: light and electron microscopic immunohistochemical studies. Brain Res. Dev. Brain Rev. 71:137–145.

    Google Scholar 

  28. Lobo, M. G. B., and Ribeiro, J. A. 1992. Effects of forskolin, dibutyryl cyclic AMP, and 5′-N-ethylcarboxamide adenosine on22Na uptake by rat brain synaptosomes stimulated by veratridine. J. Neurochem. 58:1033–1037.

    Google Scholar 

  29. Gonzales, R. A., and Moerschbaecher, J. M. 1989. A phencyclidine recognition site is associated with N-methyl-D-aspartate inhibition of carbachol-stimulated phosphoinositide hydrolysis in rat cortical slices. Mol. Pharmacol. 35:787–794.

    Google Scholar 

  30. Gusovsky, F., Hollingsworth, E. B., and Daly, J. W. 1986. Regulation of phosphatidylinositol turnover in brain synapto-neurosomes: stimulatory effects of agents that enhance influx of sodium ions. Proc. Natl. Acad. Sci. USA 83:3003–3007.

    Google Scholar 

  31. Cohen-Armon, M., Kloog, Y., Henis, Y. I., and Sokolovsky, M. 1985. Batrachotoxin changes the properties of the muscarinic receptor in rat brain and heart: Possible interaction(s) between muscarinic receptors and sodium channels. Neurobiology 82: 3524–3527.

    Google Scholar 

  32. Marinetti, G. V., Morris, T. W., and Leaky, P. 1993. Effects of Ca2+, Mg2+, and Depolarizing Agents, on the32Pi-Labeling and degradation of phosphatidylinositols in rat brain synaptosomes. Neurochem. Res. 18:345–351.

    Google Scholar 

  33. Gusovsky, F., and Daly, J. W. 1988. Formation of inositol phosphates in synaptoneurosomes of guinea pig brain: stimulatory effects of receptor agonists, sodium channel agents and sodium and calcium ionophores. Neuropharmacology 27:95–105.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Suite G01, University of Tennessee, Center for the Health Sciences, 858 Madison Ave., 38163, Memphis, TN

    Marvin E. Myles, Yesim Gokmen-Polar & John N. Fain

Authors
  1. Marvin E. Myles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yesim Gokmen-Polar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John N. Fain
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Myles, M.E., Gokmen-Polar, Y. & Fain, J.N. Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate accumulation in rat brain cortical slices. Neurochem Res 20, 1057–1064 (1995). https://doi.org/10.1007/BF00995560

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00995560

Key Words

Search

Navigation