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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):222–226. doi: 10.1111/j.1476-5381.1991.tb12410.x

Effects of Ca2+ antagonists on glutamate release and Ca2+ influx in the hippocampus with in vivo intracerebral microdialysis.

Y M Lu 1, J T Zhang 1, F Q Zhao 1, Y F Qin 1
PMCID: PMC1908273  PMID: 1686204

Abstract

1. The extracellular glutamate content and Ca2+ level in vivo in rat hippocampus were measured by brain microdialysis following administration of two depolarizing agents (veratridine, KCl) and quinolinic acid (Quin). 2. The two depolarizing agents increased the extracellular glutamate level (to between 280 and 320% basal) and decreased the extracellular Ca2+ content (to 48% of basal). However, Quin did not change the glutamate level but decreased the Ca2+ content. 3. The effects of Ca2+ antagonists on the changes of glutamate and Ca2+ level were evaluated in this experimental model. At a dose of 0.5 mg kg-1, i.v., nimodipine (L-type channel blocker) did not produce significant changes in the stimulated-glutamate release. A statistically significant inhibition of Ca2+ influx was observed at a dose of 0.05 mg kg-1. In contrast, in those animals receiving the N-type Ca2+ antagonist, daurisoline (0.1, 1 or 5 mg kg-1, i.v.), a potent attenuation of both glutamate release and Ca2+ influx was found. 4. We propose that the pharmacological properties of Ca2+ influx and of neurotransmitter release differ and that nimodipine-sensitive L-type channels may not be very common in nerve terminals but are localized in cell soma. Daurisoline-sensitive N-type channels in nerve terminals have a much greater influence on excitatory amino acid release.

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Selected References

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  1. Bowman C. L., Kimelberg H. K. Excitatory amino acids directly depolarize rat brain astrocytes in primary culture. Nature. 1984 Oct 18;311(5987):656–659. doi: 10.1038/311656a0. [DOI] [PubMed] [Google Scholar]
  2. Carbone E., Lux H. D. A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones. Nature. 1984 Aug 9;310(5977):501–502. doi: 10.1038/310501a0. [DOI] [PubMed] [Google Scholar]
  3. Freedman S. B., Miller R. J. Calcium channel activation: a different type of drug action. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5580–5583. doi: 10.1073/pnas.81.17.5580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Kelly J. S., Krnjević K., Yim G. K. Unresponsive cells in cerebral cortex. Brain Res. 1967 Dec;6(4):767–769. doi: 10.1016/0006-8993(67)90132-1. [DOI] [PubMed] [Google Scholar]
  5. Lu Y. M., Liu G. Q. Effects of l-daurisoline on quinolinic acid-induced Ca2+ influx in hippocampus neurons in freely moving rats. Zhongguo Yao Li Xue Bao. 1991 Jul;12(4):301–304. [PubMed] [Google Scholar]
  6. Lu Y. M., Liu G. Q. The effects of (-)-daurisoline on Ca2+ influx in presynaptic nerve terminals. Br J Pharmacol. 1990 Sep;101(1):45–48. doi: 10.1111/j.1476-5381.1990.tb12086.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lu Y. M., Zhang J. T., Zhao F. Q., Li F. Effects of nimodipine on l-glutamate-induced seizures and Ca2+ influx in hippocampus in freely moving rats. Zhongguo Yao Li Xue Bao. 1991 Jul;12(4):297–300. [PubMed] [Google Scholar]
  8. 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]
  9. Miller R. J., Freedman S. B. Are dihydropyridine binding sites voltage sensitive calcium channels? Life Sci. 1984 Mar 26;34(13):1205–1221. doi: 10.1016/0024-3205(84)90543-5. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Mody I., Heinemann U. Laminar profiles of the changes in extracellular calcium concentration induced by repetitive stimulation and excitatory amino acids in the rat dentate gyrus. Neurosci Lett. 1986 Aug 29;69(2):137–142. doi: 10.1016/0304-3940(86)90592-6. [DOI] [PubMed] [Google Scholar]
  12. Morocutti C., Pierelli F., Sanarelli L., Stefano E., Peppe A., Mattioli G. L. Antiepileptic effects of a calcium antagonist (nimodipine) on cefazolin-induced epileptogenic foci in rabbits. Epilepsia. 1986 Sep-Oct;27(5):498–503. doi: 10.1111/j.1528-1157.1986.tb03574.x. [DOI] [PubMed] [Google Scholar]
  13. Nachshen D. A., Blaustein M. P. The effects of some organic "calcium antagonists" on calcium influx in presynaptic nerve terminals. Mol Pharmacol. 1979 Sep;16(2):576–586. [PubMed] [Google Scholar]
  14. Norris D. K., Bradford H. F. On the specificity of verapamil as a calcium channel-blocker. Biochem Pharmacol. 1985 Jun 1;34(11):1953–1956. doi: 10.1016/0006-2952(85)90314-4. [DOI] [PubMed] [Google Scholar]
  15. Nowycky M. C., Fox A. P., Tsien R. W. Long-opening mode of gating of neuronal calcium channels and its promotion by the dihydropyridine calcium agonist Bay K 8644. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2178–2182. doi: 10.1073/pnas.82.7.2178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  17. Pumplin D. W., Reese T. S., Llinás R. Are the presynaptic membrane particles the calcium channels? Proc Natl Acad Sci U S A. 1981 Nov;78(11):7210–7213. doi: 10.1073/pnas.78.11.7210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Triggle D. J., Rampe D. 1,4-Dihydropyridine activators and antagonists: structural and functional distinctions. Trends Pharmacol Sci. 1989 Dec;10(12):507–511. doi: 10.1016/0165-6147(89)90051-5. [DOI] [PubMed] [Google Scholar]
  19. Vezzani A., Wu H. Q., Angelico P., Stasi M. A., Samanin R. Quinolinic acid-induced seizures, but not nerve cell death, are associated with extracellular Ca2+ decrease assessed in the hippocampus by brain dialysis. Brain Res. 1988 Jun 28;454(1-2):289–297. doi: 10.1016/0006-8993(88)90829-3. [DOI] [PubMed] [Google Scholar]

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