Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Sep;95(1):291–299. doi: 10.1111/j.1476-5381.1988.tb16576.x

A quantitative study of the actions of excitatory amino acids and antagonists in rat hippocampal slices.

J F Blake 1, M W Brown 1, G L Collingridge 1
PMCID: PMC1854151  PMID: 3219473

Abstract

1. A quantitative pharmacological investigation of the actions of excitatory amino acids on hippocampal CA1 neurones has been made using a new slice preparation developed for grease gap recording; d.c. potential was measured across a grease barrier placed between alvear fibres and the bathing medium. 2. In Mg2+-free perfusate, N-methyl-D-aspartate (NMDA, 1-100 microM), quisqualate (1-500 microM), kainate (1-200 microM) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 1-100 microM) caused dose-dependent depolarizations. 3. The dose-response relationships were fitted to logistic expressions. The maximum responses to AMPA, NMDA and kainate were similar; their respective EC50 values were 5, 13 and 23 microM. Quisqualate had a smaller maximum; its EC50 value was 10 microM. The slopes of the dose-response relationships were different for the 4 agonists; the order of steepness of the slopes was NMDA greater than AMPA greater than kainate greater than quisqualate. 4. Similar amino acid-induced depolarizations were observed in slices of just the CA1 region or in whole slices bathed in tetrodotoxin. Isolated alvear fibres, however, were insensitive to the excitatory amino acids. 5. D-2-Amino-5-phosphonovalerate (APV, 50 microM) selectively and reversibly antagonized responses induced by NMDA (apparent pA2 = 5.21). 6. Kynurenic acid (1 mM) reversibly depressed responses to the three agonists tested. The dose-ratios for antagonism of AMPA, kainate and quisqualate were 6.9, 5.6 and 4.6 respectively. 7. This preparation has a different sensitivity profile to agonists from those of previously reported preparations of spinal cord, neocortex and cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
291

Selected References

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

  1. Burton N. R., Smith D. A., Stone T. W. The mouse neocortical slice: preparation and responses to excitatory amino acids. Comp Biochem Physiol C. 1987;88(1):47–55. doi: 10.1016/0742-8413(87)90045-4. [DOI] [PubMed] [Google Scholar]
  2. CURTIS D. R., PHILLIS J. W., WATKINS J. C. Actions of aminoacids on the isolated hemisected spinal cord of the toad. Br J Pharmacol Chemother. 1961 Jun;16:262–283. doi: 10.1111/j.1476-5381.1961.tb01086.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Childs A. M., Evans R. H., Watkins J. C. The pharmacological selectivity of three NMDA antagonists. Eur J Pharmacol. 1988 Jan 5;145(1):81–86. doi: 10.1016/0014-2999(88)90352-4. [DOI] [PubMed] [Google Scholar]
  4. Collingridge G. L., Herron C. E., Lester R. A. Synaptic activation of N-methyl-D-aspartate receptors in the Schaffer collateral-commissural pathway of rat hippocampus. J Physiol. 1988 May;399:283–300. doi: 10.1113/jphysiol.1988.sp017080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Collingridge G. L., Kehl S. J., McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol. 1983 Jan;334:33–46. doi: 10.1113/jphysiol.1983.sp014478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collingridge G. L., Kehl S. J., McLennan H. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol. 1983 Jan;334:19–31. doi: 10.1113/jphysiol.1983.sp014477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collins G. G., Surtees L. "Desensitization" of excitatory amino acid responses in the rat olfactory cortex. Neuropharmacology. 1986 Mar;25(3):231–240. doi: 10.1016/0028-3908(86)90245-5. [DOI] [PubMed] [Google Scholar]
  8. Davies J., Francis A. A., Jones A. W., Watkins J. C. 2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation. Neurosci Lett. 1981 Jan 1;21(1):77–81. doi: 10.1016/0304-3940(81)90061-6. [DOI] [PubMed] [Google Scholar]
  9. Evans R. H., Evans S. J., Pook P. C., Sunter D. C. A comparison of excitatory amino acid antagonists acting at primary afferent C fibres and motoneurones of the isolated spinal cord of the rat. Br J Pharmacol. 1987 Jul;91(3):531–537. doi: 10.1111/j.1476-5381.1987.tb11246.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evans R. H., Francis A. A., Jones A. W., Smith D. A., Watkins J. C. The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations. Br J Pharmacol. 1982 Jan;75(1):65–75. doi: 10.1111/j.1476-5381.1982.tb08758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans R. H. The effects of amino acids and antagonists on the isolated hemisected spinal cord of the immature rat. Br J Pharmacol. 1978 Feb;62(2):171–176. doi: 10.1111/j.1476-5381.1978.tb08442.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ganong A. H., Lanthorn T. H., Cotman C. W. Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res. 1983 Aug 22;273(1):170–174. doi: 10.1016/0006-8993(83)91108-3. [DOI] [PubMed] [Google Scholar]
  13. Garthwaite J., Garthwaite G., Hajós F. Amino acid neurotoxicity: relationship to neuronal depolarization in rat cerebellar slices. Neuroscience. 1986 Jun;18(2):449–460. doi: 10.1016/0306-4522(86)90165-x. [DOI] [PubMed] [Google Scholar]
  14. Harrison N. L., Simmonds M. A. Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex. Br J Pharmacol. 1985 Feb;84(2):381–391. doi: 10.1111/j.1476-5381.1985.tb12922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krogsgaard-Larsen P., Honoré T., Hansen J. J., Curtis D. R., Lodge D. New class of glutamate agonist structurally related to ibotenic acid. Nature. 1980 Mar 6;284(5751):64–66. doi: 10.1038/284064a0. [DOI] [PubMed] [Google Scholar]
  16. Martin D., Lodge D. Biphasic effect of quinolinate on frog spinal, but not rat cortical, neurones: N-methyl-D-aspartate-like depolarisation and a novel type of hyperpolarisation. Neurosci Lett. 1987 Mar 31;75(2):175–180. doi: 10.1016/0304-3940(87)90293-x. [DOI] [PubMed] [Google Scholar]
  17. Martin D., Lodge D. Ketamine acts as a non-competitive N-methyl-D-aspartate antagonist on frog spinal cord in vitro. Neuropharmacology. 1985 Oct;24(10):999–1003. doi: 10.1016/0028-3908(85)90128-5. [DOI] [PubMed] [Google Scholar]
  18. Meldrum B. Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci (Lond) 1985 Feb;68(2):113–122. doi: 10.1042/cs0680113. [DOI] [PubMed] [Google Scholar]
  19. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  20. Perkins M. N., Stone T. W. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982 Sep 9;247(1):184–187. doi: 10.1016/0006-8993(82)91048-4. [DOI] [PubMed] [Google Scholar]
  21. Surtees L., Collins G. G. Receptor types mediating the excitatory actions of exogenous L-aspartate and L-glutamate in rat olfactory cortex. Brain Res. 1985 May 20;334(2):287–295. doi: 10.1016/0006-8993(85)90220-3. [DOI] [PubMed] [Google Scholar]
  22. Swanson L. W., Wyss J. M., Cowan W. M. An autoradiographic study of the organization of intrahippocampal association pathways in the rat. J Comp Neurol. 1978 Oct 15;181(4):681–715. doi: 10.1002/cne.901810402. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Wheatley P. L., Collins K. J. Quantitative studies of N-methyl-D-aspartate, 2-amino-5-phosphonovalerate and cis-2,3-piperidine dicarboxylate interactions on the neonatal rat spinal cord in vitro. Eur J Pharmacol. 1986 Feb 18;121(2):257–263. doi: 10.1016/0014-2999(86)90497-8. [DOI] [PubMed] [Google Scholar]
  25. 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]

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

RESOURCES