Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 May;112(1):231–239. doi: 10.1111/j.1476-5381.1994.tb13057.x

Modulatory effects of NMDA on phosphoinositide responses evoked by the metabotropic glutamate receptor agonist 1S,3R-ACPD in neonatal rat cerebral cortex.

R A Challiss 1, R Mistry 1, D W Gray 1, S R Nahorski 1
PMCID: PMC1910290  PMID: 7913380

Abstract

1. The effect of NMDA-receptor stimulation on phosphoinositide signalling in response to the metabotropic glutamate receptor agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) has been examined in neonatal rat cerebral cortex slices. 2. Total [3H]-inositol phosphate ([3H]-InsPx) accumulation, in the presence of 5 mM LiCl, in [3H]-inositol pre-labelled slices was concentration-dependently increased by 1S,3R-ACPD (EC50 16.6 microM) and, at a maximally effective concentration, 1S,3R-ACPD (300 microM) increased [3H]-InsPx accumulation by 12.8 fold over basal values. 3. [3H]-InsPx accumulation stimulated by 1S,1R-ACPD was enhanced by low concentrations of NMDA (3-30 microM), but not by higher concentrations (> 30 microM). [3H]-InsPx accumulations stimulated by 1S,3R-ACPD in the absence or presence of 10 microM NMDA were linear with time, at least over the 15 min period examined; however, in the presence of 100 microM NMDA the initial enhancement of 1S,3R-ACPD-stimulated phosphoinositide hydrolysis progressively decreased with time. 4. In the presence of a maximal enhancing concentration of NMDA (10 microM), the response to 1S,3R-ACPD (300 microM) was increased 1.9 fold and the EC50 for agonist-stimulated [3H]-InsPx accumulation decreased about 4 fold. The enhanced response to the metabotropic agonist was concentration-dependently inhibited by competitive and uncompetitive antagonists of NMDA-receptor activation. 5. 1S,3R-ACPD also stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) mass accumulation with an initial peak response (5-6 fold over basal) at 15 s decaying to a smaller (2 fold), but persistent elevated accumulation (1-10 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
231

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe T., Sugihara H., Nawa H., Shigemoto R., Mizuno N., Nakanishi S. Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. J Biol Chem. 1992 Jul 5;267(19):13361–13368. [PubMed] [Google Scholar]
  2. Aramori I., Nakanishi S. Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron. 1992 Apr;8(4):757–765. doi: 10.1016/0896-6273(92)90096-v. [DOI] [PubMed] [Google Scholar]
  3. Baird J. G., Challiss R. A., Nahorski S. R. Role for ionotropic and metabotropic receptors in quisqualate-stimulated inositol polyphosphate accumulation in rat cerebral cortex. Mol Pharmacol. 1991 Jun;39(6):745–753. [PubMed] [Google Scholar]
  4. Baird J. G., Nahorski S. R. Increased intracellular calcium stimulates 3H-inositol polyphosphate accumulation in rat cerebral cortical slices. J Neurochem. 1990 Feb;54(2):555–561. doi: 10.1111/j.1471-4159.1990.tb01907.x. [DOI] [PubMed] [Google Scholar]
  5. Baird J. G., Nahorski S. R. Stimulatory and inhibitory effects of N-methyl-D-aspartate on 3H-inositol polyphosphate accumulation in rat cortical slices. J Neurochem. 1991 Aug;57(2):629–635. doi: 10.1111/j.1471-4159.1991.tb03794.x. [DOI] [PubMed] [Google Scholar]
  6. Bashir Z. I., Bortolotto Z. A., Davies C. H., Berretta N., Irving A. J., Seal A. J., Henley J. M., Jane D. E., Watkins J. C., Collingridge G. L. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature. 1993 May 27;363(6427):347–350. doi: 10.1038/363347a0. [DOI] [PubMed] [Google Scholar]
  7. Baskys A., Malenka R. C. Agonists at metabotropic glutamate receptors presynaptically inhibit EPSCs in neonatal rat hippocampus. J Physiol. 1991 Dec;444:687–701. doi: 10.1113/jphysiol.1991.sp018901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Baudry M., Evans J., Lynch G. Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonists in hippocampus. Nature. 1986 Jan 23;319(6051):329–331. doi: 10.1038/319329a0. [DOI] [PubMed] [Google Scholar]
  9. Beal M. F. Role of excitotoxicity in human neurological disease. Curr Opin Neurobiol. 1992 Oct;2(5):657–662. doi: 10.1016/0959-4388(92)90035-j. [DOI] [PubMed] [Google Scholar]
  10. Behnisch T., Reymann K. G. Co-activation of metabotropic glutamate and N-methyl-D-aspartate receptors is involved in mechanisms of long-term potentiation maintenance in rat hippocampal CA1 neurons. Neuroscience. 1993 May;54(1):37–47. doi: 10.1016/0306-4522(93)90381-o. [DOI] [PubMed] [Google Scholar]
  11. Bekkers J. M., Stevens C. F. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature. 1989 Sep 21;341(6239):230–233. doi: 10.1038/341230a0. [DOI] [PubMed] [Google Scholar]
  12. Birrell G. J., Marcoux F. W. Excitatory amino acid receptor-stimulated phosphoinositide turnover in primary cerebrocortical cultures. Br J Pharmacol. 1993 Jun;109(2):379–385. doi: 10.1111/j.1476-5381.1993.tb13580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bleakman D., Rusin K. I., Chard P. S., Glaum S. R., Miller R. J. Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn. Mol Pharmacol. 1992 Aug;42(2):192–196. [PubMed] [Google Scholar]
  14. Challiss R. A., Batty I. H., Nahorski S. R. Mass measurements of inositol(1,4,5)trisphosphate in rat cerebral cortex slices using a radioreceptor assay: effects of neurotransmitters and depolarization. Biochem Biophys Res Commun. 1988 Dec 15;157(2):684–691. doi: 10.1016/s0006-291x(88)80304-8. [DOI] [PubMed] [Google Scholar]
  15. Challiss R. A., Nahorski S. R. 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. 1991 Sep;57(3):1042–1051. doi: 10.1111/j.1471-4159.1991.tb08255.x. [DOI] [PubMed] [Google Scholar]
  16. Chen L., Huang L. Y. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature. 1992 Apr 9;356(6369):521–523. doi: 10.1038/356521a0. [DOI] [PubMed] [Google Scholar]
  17. Choi D. W. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci. 1988 Oct;11(10):465–469. doi: 10.1016/0166-2236(88)90200-7. [DOI] [PubMed] [Google Scholar]
  18. Courtney M. J., Nicholls D. G. Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses. J Neurochem. 1992 Sep;59(3):983–992. doi: 10.1111/j.1471-4159.1992.tb08339.x. [DOI] [PubMed] [Google Scholar]
  19. Dickenson J. M., Hill S. J. Adenosine A1-receptor stimulated increases in intracellular calcium in the smooth muscle cell line, DDT1MF-2. Br J Pharmacol. 1993 Jan;108(1):85–92. doi: 10.1111/j.1476-5381.1993.tb13444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Eberhard D. A., Holz R. W. Intracellular Ca2+ activates phospholipase C. Trends Neurosci. 1988 Dec;11(12):517–520. doi: 10.1016/0166-2236(88)90174-9. [DOI] [PubMed] [Google Scholar]
  22. Fotuhi M., Sharp A. H., Glatt C. E., Hwang P. M., von Krosigk M., Snyder S. H., Dawson T. M. Differential localization of phosphoinositide-linked metabotropic glutamate receptor (mGluR1) and the inositol 1,4,5-trisphosphate receptor in rat brain. J Neurosci. 1993 May;13(5):2001–2012. doi: 10.1523/JNEUROSCI.13-05-02001.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Frandsen A., Schousboe A. Excitatory amino acid-mediated cytotoxicity and calcium homeostasis in cultured neurons. J Neurochem. 1993 Apr;60(4):1202–1211. doi: 10.1111/j.1471-4159.1993.tb03278.x. [DOI] [PubMed] [Google Scholar]
  24. Gasic G. P., Hollmann M. Molecular neurobiology of glutamate receptors. Annu Rev Physiol. 1992;54:507–536. doi: 10.1146/annurev.ph.54.030192.002451. [DOI] [PubMed] [Google Scholar]
  25. Godfrey P. P., Wilkins C. J., Tyler W., Watson S. P. Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rat cerebral cortex. Br J Pharmacol. 1988 Sep;95(1):131–138. doi: 10.1111/j.1476-5381.1988.tb16556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gonzales R. A., Moerschbaecher J. M. A phencyclidine recognition site is associated with N-methyl-D-aspartate inhibition of carbachol-stimulated phosphoinositide hydrolysis in rat cortical slices. Mol Pharmacol. 1989 Jun;35(6):787–794. [PubMed] [Google Scholar]
  27. Harvey J., Collingridge G. L. Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices. Br J Pharmacol. 1993 Aug;109(4):1085–1090. doi: 10.1111/j.1476-5381.1993.tb13733.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Irving A. J., Collingridge G. L., Schofield J. G. L-glutamate and acetylcholine mobilise Ca2+ from the same intracellular pool in cerebellar granule cells using transduction mechanisms with different Ca2+ sensitivities. Cell Calcium. 1992 May;13(5):293–301. doi: 10.1016/0143-4160(92)90064-y. [DOI] [PubMed] [Google Scholar]
  29. Irving A. J., Schofield J. G., Watkins J. C., Sunter D. C., Collingridge G. L. 1S,3R-ACPD stimulates and L-AP3 blocks Ca2+ mobilization in rat cerebellar neurons. Eur J Pharmacol. 1990 Sep 21;186(2-3):363–365. doi: 10.1016/0014-2999(90)90462-f. [DOI] [PubMed] [Google Scholar]
  30. Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
  31. Jones K. A., Baughman R. W. Both NMDA and non-NMDA subtypes of glutamate receptors are concentrated at synapses on cerebral cortical neurons in culture. Neuron. 1991 Oct;7(4):593–603. doi: 10.1016/0896-6273(91)90372-7. [DOI] [PubMed] [Google Scholar]
  32. Kelso S. R., Nelson T. E., Leonard J. P. Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes. J Physiol. 1992 Apr;449:705–718. doi: 10.1113/jphysiol.1992.sp019110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kemp J. A., Leeson P. D. The glycine site of the NMDA receptor--five years on. Trends Pharmacol Sci. 1993 Jan;14(1):20–25. doi: 10.1016/0165-6147(93)90108-v. [DOI] [PubMed] [Google Scholar]
  34. Madison D. V., Malenka R. C., Nicoll R. A. Mechanisms underlying long-term potentiation of synaptic transmission. Annu Rev Neurosci. 1991;14:379–397. doi: 10.1146/annurev.ne.14.030191.002115. [DOI] [PubMed] [Google Scholar]
  35. Martin L. J., Blackstone C. D., Huganir R. L., Price D. L. Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron. 1992 Aug;9(2):259–270. doi: 10.1016/0896-6273(92)90165-a. [DOI] [PubMed] [Google Scholar]
  36. Masu M., Tanabe Y., Tsuchida K., Shigemoto R., Nakanishi S. Sequence and expression of a metabotropic glutamate receptor. Nature. 1991 Feb 28;349(6312):760–765. doi: 10.1038/349760a0. [DOI] [PubMed] [Google Scholar]
  37. Morrisett R. A., Chow C. C., Sakaguchi T., Shin C., McNamara J. O. Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation. J Neurochem. 1990 May;54(5):1517–1525. doi: 10.1111/j.1471-4159.1990.tb01199.x. [DOI] [PubMed] [Google Scholar]
  38. Nakanishi S. Molecular diversity of glutamate receptors and implications for brain function. Science. 1992 Oct 23;258(5082):597–603. doi: 10.1126/science.1329206. [DOI] [PubMed] [Google Scholar]
  39. Nicholls D. G. Neurotransmission. A retrograde step forward. Nature. 1992 Nov 12;360(6400):106–107. doi: 10.1038/360106a0. [DOI] [PubMed] [Google Scholar]
  40. Nicoletti F., Meek J. L., Iadarola M. J., Chuang D. M., Roth B. L., Costa E. Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem. 1986 Jan;46(1):40–46. doi: 10.1111/j.1471-4159.1986.tb12922.x. [DOI] [PubMed] [Google Scholar]
  41. Palmer E., Monaghan D. T., Cotman C. W. Glutamate receptors and phosphoinositide metabolism: stimulation via quisqualate receptors is inhibited by N-methyl-D-aspartate receptor activation. Brain Res. 1988 Sep;464(2):161–165. doi: 10.1016/0169-328x(88)90008-3. [DOI] [PubMed] [Google Scholar]
  42. Pickering D. S., Thomsen C., Suzdak P. D., Fletcher E. J., Robitaille R., Salter M. W., MacDonald J. F., Huang X. P., Hampson D. R. A comparison of two alternatively spliced forms of a metabotropic glutamate receptor coupled to phosphoinositide turnover. J Neurochem. 1993 Jul;61(1):85–92. doi: 10.1111/j.1471-4159.1993.tb03540.x. [DOI] [PubMed] [Google Scholar]
  43. Randall R. D., Thayer S. A. Glutamate-induced calcium transient triggers delayed calcium overload and neurotoxicity in rat hippocampal neurons. J Neurosci. 1992 May;12(5):1882–1895. doi: 10.1523/JNEUROSCI.12-05-01882.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schmidt B. H., Weiss S., Sebben M., Kemp D. E., Bockaert J., Sladeczek F. Dual action of excitatory amino acids on the metabolism of inositol phosphates in striatal neurons. Mol Pharmacol. 1987 Sep;32(3):364–368. [PubMed] [Google Scholar]
  45. Schoepp D. D., Johnson B. G. Excitatory amino acid agonist-antagonist interactions at 2-amino-4-phosphonobutyric acid-sensitive quisqualate receptors coupled to phosphoinositide hydrolysis in slices of rat hippocampus. J Neurochem. 1988 May;50(5):1605–1613. doi: 10.1111/j.1471-4159.1988.tb03050.x. [DOI] [PubMed] [Google Scholar]
  46. Sladeczek F., Pin J. P., Récasens M., Bockaert J., Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature. 1985 Oct 24;317(6039):717–719. doi: 10.1038/317717a0. [DOI] [PubMed] [Google Scholar]
  47. Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S. A family of metabotropic glutamate receptors. Neuron. 1992 Jan;8(1):169–179. doi: 10.1016/0896-6273(92)90118-w. [DOI] [PubMed] [Google Scholar]
  48. Wojcikiewicz R. J., Tobin A. B., Nahorski S. R. Desensitization of cell signalling mediated by phosphoinositidase C. Trends Pharmacol Sci. 1993 Jul;14(7):279–285. doi: 10.1016/0165-6147(93)90131-3. [DOI] [PubMed] [Google Scholar]
  49. Zheng F., Gallagher J. P. Metabotropic glutamate receptors are required for the induction of long-term potentiation. Neuron. 1992 Jul;9(1):163–172. doi: 10.1016/0896-6273(92)90231-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES