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PMID: 8395285 Published · ppublish English Journal Article

Excitatory amino acid receptor-stimulated phosphoinositide turnover in primary cerebrocortical cultures.

British journal of pharmacology ·Vol. 109 ·No. 2 ·1993-06-00 ·Pages 379-85

Birrell GJ, Marcoux FW

Abstract

1. Characterization of excitatory amino acid-induced accumulation of [3H]-phosphoinositides was carried out in primary cerebrocortical cultures isolated from foetal rats. 2. All of the excitatory amino acid receptor agonists examined caused concentration-dependent enhancement of phosphoinositide (PI) formation. The most potent excitatory amino acid receptor agonists were quisqualate, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD), ibotenate and glutamate with mean EC50 values of 0.9 +/- 0.4 microM, 15 +/- 5 microM, 15 +/- 3 microM and 41 +/- 8 microM respectively. 3. The selective ionotropic receptor antagonists kynurenic acid (1 mM), 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX, 10 microM) and (+/-)-4-(3-phosphonopropyl)-2 piperazinecarboxylic acid (CPP, 100 microM), failed to block responses to quisqualate, (1S,3R)-ACPD or glutamate. D,L-2-Amino-3-phosphonopropionate (D,L-AP3) did not block 1S,3R-ACPD or quisqualate-induced PI turnover, but had an additive effect with quisqualate or (1S,3R)-ACPD. 4. Exposure of cultures to agonists in the absence of added extracellular calcium reduced the maximal quisqualate response by approximately 45%, revealing a two-component concentration-response curve. Concentration-response curves to ibotenate and glutamate became flattened by omission of extracellular calcium, whereas (1S,3R)-ACPD-stimulated PI turnover was unaffected. 5. Pretreatment of cultures with pertussis toxin markedly inhibited PI responses evoked by (1S,3R)-ACPD. 6. These results suggest that excitatory amino acid-stimulated PI turnover in cerebrocortical cultures is independent of ionotropic receptor activation and is mediated via specific G-protein-linked metabotropic receptors. The partial dependence of the responses to quisqualate, ibotenate and glutamate on the presence of extracellular calcium suggests that the effects of these agonists may be mediated by more than one receptor subtype.

MeSH Terms
Animals Calcium/physiology Cells, Cultured Cerebral Cortex/metabolism Cycloleucine/analogs & derivatives,pharmacology Female GTP-Binding Proteins/metabolism Kynurenic Acid/pharmacology Pertussis Toxin Phosphatidylinositols/metabolism Piperazines/pharmacology Pregnancy Quinoxalines/pharmacology Quisqualic Acid/pharmacology Rats Receptors, Amino Acid/metabolism Receptors, Glutamate/drug effects Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors Virulence Factors, Bordetella/pharmacology
Chemicals
Phosphatidylinositols Piperazines Quinoxalines Receptors, Amino Acid Receptors, Glutamate Receptors, N-Methyl-D-Aspartate Virulence Factors, Bordetella Cycloleucine 1-amino-1,3-dicarboxycyclopentane 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline Quisqualic Acid 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid Pertussis Toxin GTP-Binding Proteins Kynurenic Acid Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Birrell G J
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48106.
Marcoux F W
References (49)
49 references, click to expand
  1. The activation of inositol phospholipid metabolism as a signal-transducing system for excitatory amino acids in primary cultures of cerebellar granule cells.
    J Neurosci. 1986 Jul;6(7):1905-11 PMID: 3016212
  2. (2S,3S,4S) alpha-(carboxycyclopropyl)glycine is a novel agonist of metabotropic glutamate receptors.
    Eur J Pharmacol. 1990 Aug 2;184(1):205-6 PMID: 1976529
  3. A new type of glutamate receptor linked to inositol phospholipid metabolism.
    Nature. 1987 Feb 5-11;325(6104):531-3 PMID: 2880300
  4. Characterization of subtypes of excitatory amino acid receptors involved in the stimulation of inositol phosphate synthesis in rat brain synaptoneurosomes.
    Eur J Pharmacol. 1987 Sep 2;141(1):87-93 PMID: 2822447
  5. Dual action of excitatory amino acids on the metabolism of inositol phosphates in striatal neurons.
    Mol Pharmacol. 1987 Sep;32(3):364-8 PMID: 2890092
  6. 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):1605-13 PMID: 2834517
  7. Pertussis toxin inhibits signal transduction at a specific metabolotropic glutamate receptor in primary cultures of cerebellar granule cells.
    Neuropharmacology. 1988 Jun;27(6):551-6 PMID: 2843781
  8. Excitatory amino acids inhibit stimulated phosphoinositide hydrolysis in the rat prefrontal cortex.
    Life Sci. 1989;44(1):19-26 PMID: 2563300
  9. Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rat cerebral cortex.
    Br J Pharmacol. 1988 Sep;95(1):131-8 PMID: 2464383
  10. Glutamate receptors and phosphoinositide metabolism: stimulation via quisqualate receptors is inhibited by N-methyl-D-aspartate receptor activation.
    Brain Res. 1988 Sep;464(2):161-5 PMID: 2905924
  11. Kynurenic acid inhibits the activation of kainic and N-methyl-D-aspartic acid-sensitive ionotropic receptors by a different mechanism.
    Neuropharmacology. 1989 May;28(5):453-7 PMID: 2471112
  12. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system.
    Annu Rev Pharmacol Toxicol. 1989;29:365-402 PMID: 2543272
  13. 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):787-94 PMID: 2543912
  14. Developmental changes in the chemosensitivity of rat brain synaptoneurosomes to excitatory amino acids, estimated by inositol phosphate formation.
    Int J Dev Neurosci. 1989;7(3):257-66 PMID: 2569258
  15. Muscarinic and quisqualate receptor-induced phosphoinositide hydrolysis in primary cultures of striatal and hippocampal neurons. Evidence for differential mechanisms of activation.
    J Neurochem. 1989 Sep;53(3):825-33 PMID: 2547903
  16. Trans-ACPD, a selective agonist of the phosphoinositide-coupled excitatory amino acid receptor.
    Eur J Pharmacol. 1989 Aug 3;166(3):585-7 PMID: 2553440
  17. Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the neonatal rat hippocampus by 2-amino-3-phosphonopropionate.
    J Neurochem. 1989 Dec;53(6):1865-70 PMID: 2572680
  18. Intracellular calcium mobilization triggered by a glutamate receptor in rat cultured hippocampal cells.
    J Physiol. 1989 Jul;414:539-48 PMID: 2575164
  19. Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists.
    Trends Pharmacol Sci. 1990 Jan;11(1):25-33 PMID: 2155495
  20. Characterization of the quisqualate receptor linked to phosphoinositide hydrolysis in neurocortical cultures.
    J Neurochem. 1990 May;54(5):1461-6 PMID: 2157812
  21. Inhibition of muscarinic-coupled phosphoinositide hydrolysis by N-methyl-D-aspartate is dependent on depolarization via channel activation.
    J Neurochem. 1990 May;54(5):1517-25 PMID: 1691275
  22. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death.
    Annu Rev Neurosci. 1990;13:171-82 PMID: 1970230
  23. Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rabbit retina. Evidence for a specific quisqualate receptor subtype associated with neurones.
    Exp Eye Res. 1990 Apr;50(4):397-405 PMID: 2159888
  24. Stereoselectivity and mode of inhibition of phosphoinositide-coupled excitatory amino acid receptors by 2-amino-3-phosphonopropionic acid.
    Mol Pharmacol. 1990 Aug;38(2):222-8 PMID: 2166902
  25. Increased brain myo-inositol 1-phosphate in lithium-treated rats.
    Biochem Biophys Res Commun. 1976 Jul 26;71(2):664-70 PMID: 962945
  26. Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.
    J Neurophysiol. 1977 Sep;40(5):1132-50 PMID: 333062
  27. Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands.
    Biochem J. 1982 Sep 15;206(3):587-95 PMID: 7150264
  28. Glutamate stimulates inositol phosphate formation in striatal neurones.
    Nature. 1985 Oct 24-30;317(6039):717-9 PMID: 2865680
  29. Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus.
    J Neurochem. 1986 Jan;46(1):40-6 PMID: 2866236
  30. Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonists in hippocampus.
    Nature. 1986 Jan 23-29;319(6051):329-31 PMID: 2867474
  31. Excitatory amino acid recognition sites coupled with inositol phospholipid metabolism: developmental changes and interaction with alpha 1-adrenoceptors.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1931-5 PMID: 2869493
  32. Autoradiographic imaging of phosphoinositide turnover in the brain.
    Science. 1990 Aug 17;249(4970):802-4 PMID: 1975122
  33. Inositol trisphosphate and diacylglycerol: two interacting second messengers.
    Annu Rev Biochem. 1987;56:159-93 PMID: 3304132
  34. G proteins: transducers of receptor-generated signals.
    Annu Rev Biochem. 1987;56:615-49 PMID: 3113327
  35. How far does phospholipase C activity depend on the cell calcium concentration? A study in intact cells.
    Biochem J. 1987 Apr 15;243(2):391-8 PMID: 2820378
  36. Purification and characterization of a phosphoinositide-specific phospholipase C from guinea pig uterus. Phosphorylation by protein kinase C in vivo.
    J Biol Chem. 1987 Oct 5;262(28):13789-97 PMID: 2820980
  37. Purification of phosphoinositide-specific phospholipase C from a particulate fraction of bovine brain.
    Eur J Biochem. 1987 Oct 15;168(2):413-8 PMID: 2822416
  38. Excitatory amino acid neurotoxicity and neurodegenerative disease.
    Trends Pharmacol Sci. 1990 Sep;11(9):379-87 PMID: 2238094
  39. Sequence and expression of a metabotropic glutamate receptor.
    Nature. 1991 Feb 28;349(6312):760-5 PMID: 1847995
  40. Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors.
    Trends Pharmacol Sci. 1990 Dec;11(12):508-15 PMID: 1964257
  41. Stimulatory and inhibitory effects of N-methyl-D-aspartate on 3H-inositol polyphosphate accumulation in rat cortical slices.
    J Neurochem. 1991 Aug;57(2):629-35 PMID: 2072107
  42. Pharmacological characterization of the quisqualate receptor coupled to phospholipase C (Qp) in striatal neurons.
    Eur J Pharmacol. 1991 Jul 12;207(3):231-41 PMID: 1680062
  43. Inhibitory effect of NMDA receptor activation on quisqualate-stimulated phosphatidylinositol turnover in the human cerebral cortex.
    Brain Res. 1991 Jul 5;553(1):14-7 PMID: 1834301
  44. Excitatory amino acids: new tools for old stories or pharmacological subtypes of glutamate receptors: electrophysiological studies.
    Can J Physiol Pharmacol. 1991 Jul;69(7):1123-8 PMID: 1659489
  45. Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders.
    Brain Res Brain Res Rev. 1991 May-Aug;16(2):171-91 PMID: 1662102
  46. A family of metabotropic glutamate receptors.
    Neuron. 1992 Jan;8(1):169-79 PMID: 1309649
  47. Structure-activity analysis of binding kinetics for NMDA receptor competitive antagonists: the influence of conformational restriction.
    Br J Pharmacol. 1991 Sep;104(1):207-21 PMID: 1686203
  48. Metabotropic receptors and 'slow' excitatory actions of glutamate agonists in the hippocampus.
    Trends Neurosci. 1992 Mar;15(3):92-6 PMID: 1373924
  49. Magnesium ions inhibit the stimulation of inositol phospholipid hydrolysis by endogenous excitatory amino acids in primary cultures of cerebellar granule cells.
    J Neurochem. 1987 Mar;48(3):967-73 PMID: 2879893
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1111/j.1476-5381.1993.tb13580.x
Published
1993-06-00
Pages
379-85
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2175676
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.1993.tb13580.x PMC Full Text View journal details
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