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. 1989 Nov;98(3):767–772. doi: 10.1111/j.1476-5381.1989.tb14604.x

Inhibition of N-methyl-D-aspartate- and kainic acid-induced neurotransmitter release by omega-conotoxin GVIA.

R A Keith 1, T J Mangano 1, A I Salama 1
PMCID: PMC1854761  PMID: 2574063

Abstract

1. The role of voltage-sensitive calcium channels (VSCC) in N-methyl-D-aspartate (NMDA)- and kainic acid (KA)-evoked neurotransmitter release from rat cortical and hippocampal brain slices was evaluated by determining the effects of omega-conotoxin GVIA, an inhibitor of neuronal L- and N-type VSCC, and PN 200-110, a selective inhibitor of L-type VSCC. 2. Selective antagonists of the NMDA receptor ionophore complex, Mg2+, CPP and MK-801, inhibited NMDA- but not KA-evoked release of [3H]-noradrenaline from hippocampal and cortical brain slices. This suggests that cortical and hippocampal receptors are similar and that NMDA and KA act at distinct excitatory amino acid receptor subtypes. 3. [3H]-noradrenaline release induced by both NMDA and KA was similarly inhibited (approximately 30%) by omega-conotoxin GVIA. In contrast, PN 200-110 had no significant effect, although there was a tendency towards inhibition. 4. The results suggest that although NMDA- and KA-receptors are pharmacologically distinct, the N-type, but not the L-type, VSCC plays a small but significant role in neurotransmitter release induced by both NMDA and KA. It remains to be determined whether the N-type VSCC are involved in the physiological and/or pathological manifestations of excitatory amino acid receptor stimulation.

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Selected References

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  1. Abe T., Koyano K., Saisu H., Nishiuchi Y., Sakakibara S. Binding of omega-conotoxin to receptor sites associated with the voltage-sensitive calcium channel. Neurosci Lett. 1986 Nov 11;71(2):203–208. doi: 10.1016/0304-3940(86)90559-8. [DOI] [PubMed] [Google Scholar]
  2. Ascher P., Nowak L. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol. 1988 May;399:247–266. doi: 10.1113/jphysiol.1988.sp017078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davies J., Evans R. H., Herrling P. L., Jones A. W., Olverman H. J., Pook P., Watkins J. C. CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]D-AP5 binding sites on brain membranes and anticonvulsant activity. Brain Res. 1986 Sep 10;382(1):169–173. doi: 10.1016/0006-8993(86)90127-7. [DOI] [PubMed] [Google Scholar]
  4. Dingledine R. N-methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells. J Physiol. 1983 Oct;343:385–405. doi: 10.1113/jphysiol.1983.sp014899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Feigenbaum P., Garcia M. L., Kaczorowski G. J. Evidence for distinct sites coupled to high affinity omega-conotoxin receptors in rat brain synaptic plasma membrane vesicles. Biochem Biophys Res Commun. 1988 Jul 15;154(1):298–305. doi: 10.1016/0006-291x(88)90684-5. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Jones S. M., Snell L. D., Johnson K. M. Phencyclidine selectively inhibits N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release. J Pharmacol Exp Ther. 1987 Feb;240(2):492–497. [PubMed] [Google Scholar]
  9. Keith R. A., Mangano T. J., Pacheco M. A., Salama A. I. Characterization of the effects of omega-conotoxin GVIA on the responses of voltage-sensitive calcium channels. J Auton Pharmacol. 1989 Aug;9(4):243–252. doi: 10.1111/j.1474-8673.1989.tb00215.x. [DOI] [PubMed] [Google Scholar]
  10. Kleckner N. W., Dingledine R. Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science. 1988 Aug 12;241(4867):835–837. doi: 10.1126/science.2841759. [DOI] [PubMed] [Google Scholar]
  11. Lalies M., Middlemiss D. N., Ransom R. Stereoselective antagonism of NMDA-stimulated noradrenaline release from rat hippocampal slices by MK-801. Neurosci Lett. 1988 Sep 12;91(3):339–342. doi: 10.1016/0304-3940(88)90703-3. [DOI] [PubMed] [Google Scholar]
  12. Lazarewicz J. W., Lehmann A., Hagberg H., Hamberger A. Effects of kainic acid on brain calcium fluxes studied in vivo and in vitro. J Neurochem. 1986 Feb;46(2):494–498. doi: 10.1111/j.1471-4159.1986.tb12995.x. [DOI] [PubMed] [Google Scholar]
  13. Lee H. R., Roeske W. R., Yamamura H. I. High affinity specific [3H](+)PN 200-110 binding to dihydropyridine receptors associated with calcium channels in rat cerebral cortex and heart. Life Sci. 1984 Aug 13;35(7):721–732. doi: 10.1016/0024-3205(84)90340-0. [DOI] [PubMed] [Google Scholar]
  14. Lehmann J., Ferkany J. W., Schaeffer P., Coyle J. T. Dissociation between the excitatory and "excitotoxic" effects of quinolinic acid analogs on the striatal cholinergic interneuron. J Pharmacol Exp Ther. 1985 Mar;232(3):873–882. [PubMed] [Google Scholar]
  15. Lehmann J., Scatton B. Characterization of the excitatory amino acid receptor-mediated release of [3H]acetylcholine from rat striatal slices. Brain Res. 1982 Dec 2;252(1):77–89. doi: 10.1016/0006-8993(82)90980-5. [DOI] [PubMed] [Google Scholar]
  16. MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., Barker J. L. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. 1986 May 29-Jun 4Nature. 321(6069):519–522. doi: 10.1038/321519a0. [DOI] [PubMed] [Google Scholar]
  17. Mayer M. L., Westbrook G. L., Guthrie P. B. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature. 1984 May 17;309(5965):261–263. doi: 10.1038/309261a0. [DOI] [PubMed] [Google Scholar]
  18. Mayer M. L., Westbrook G. L. Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol. 1987 Dec;394:501–527. doi: 10.1113/jphysiol.1987.sp016883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miller R. J. Multiple calcium channels and neuronal function. Science. 1987 Jan 2;235(4784):46–52. doi: 10.1126/science.2432656. [DOI] [PubMed] [Google Scholar]
  20. Pastuszko A., Wilson D. F., Erecińska M. Effects of kainic acid in rat brain synaptosomes: the involvement of calcium. J Neurochem. 1984 Sep;43(3):747–754. doi: 10.1111/j.1471-4159.1984.tb12796.x. [DOI] [PubMed] [Google Scholar]
  21. Riveros N., Orrego F. N-methylaspartate-activated calcium channels in rat brain cortex slices. Effect of calcium channel blockers and of inhibitory and depressant substances. Neuroscience. 1986 Mar;17(3):541–546. doi: 10.1016/0306-4522(86)90029-1. [DOI] [PubMed] [Google Scholar]
  22. SHANES A. M. Electrochemical aspects of physiological and pharmacological action in excitable cells. I. The resting cell and its alteration by extrinsic factors. Pharmacol Rev. 1958 Mar;10(1):59–164. [PubMed] [Google Scholar]
  23. Schmidt C. J., Taylor V. L. Release of [3H]norepinephrine from rat hippocampal slices by N-methyl-D-aspartate: comparison of the inhibitory effects of Mg2+ and MK-801. Eur J Pharmacol. 1988 Oct 26;156(1):111–120. doi: 10.1016/0014-2999(88)90153-7. [DOI] [PubMed] [Google Scholar]
  24. Snell L. D., Johnson K. M. Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs. J Pharmacol Exp Ther. 1986 Sep;238(3):938–946. [PubMed] [Google Scholar]
  25. Wagner J. A., Snowman A. M., Biswas A., Olivera B. M., Snyder S. H. Omega-conotoxin GVIA binding to a high-affinity receptor in brain: characterization, calcium sensitivity, and solubilization. J Neurosci. 1988 Sep;8(9):3354–3359. doi: 10.1523/JNEUROSCI.08-09-03354.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
  27. Watkins J. C., Evans R. H. Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol. 1981;21:165–204. doi: 10.1146/annurev.pa.21.040181.001121. [DOI] [PubMed] [Google Scholar]
  28. Wong E. H., Kemp J. A., Priestley T., Knight A. R., Woodruff G. N., Iversen L. L. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7104–7108. doi: 10.1073/pnas.83.18.7104. [DOI] [PMC free article] [PubMed] [Google Scholar]

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