Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jan;108(1):179–184. doi: 10.1111/j.1476-5381.1993.tb13459.x

A comparison of the actions of agonists and antagonists at non-NMDA receptors of C fibres and motoneurones of the immature rat spinal cord in vitro.

P Pook 1, F Brugger 1, N S Hawkins 1, K C Clark 1, J C Watkins 1, R H Evans 1
PMCID: PMC1907711  PMID: 8094024

Abstract

1. The shift in d.c. potential in dorsal roots (EC50 8.0 microM +/- 0.9 s.e. mean, n = 5) or depression of the C elevation of the compound action potential (EC50 3.0 microM +/- 0.3, n = 7) have been used to measure the depolarizing action of kainate on dorsal root C fibres of immature (3 to 5 day old) rats. Depolarization of motoneurones was measured from the shift in d.c. potential in ventral roots. 2. 6-Cyano-7-nitroquinoxaline,2-3,dione (CNQX) (pA2 5.78 +/- 0.06, n = 8) and 6-nitro-7-suplhamobenzo(f)quinoxaline-2,3-dione (NBQX) (pA2 5.75 +/- 0.04, n = 7) had similar potencies as antagonists of kainate at dorsal root fibres. The potency of NBQX as a kainate antagonist was similar also at motoneurones (pA2 5.72 +/- 0.07, n = 3). At motoneurones, NBQX was less potent as an antagonist of domoate (pA2 5.29 +/- 0.05) and more potent as an antagonist of S-alpha-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (pA2 6.80 +/- 0.09) than as an antagonist of kainate. 3. Application of L-glutamate, quisqualate and RS-AMPA to dorsal roots produced only short lasting depolarizations but kainate concentration-effect plots were shifted to the right in the presence of these three agonists (pA2 5.08 +/- 0.08, (n = 3), 5.59 +/- 0.04, (n = 4) and 4.46 +/- 0.04 (n = 4) respectively). Slopes of dose-ratio against concentration were significantly less than one for the latter antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
179

Selected References

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

  1. Agrawal S. G., Evans R. H. The primary afferent depolarizing action of kainate in the rat. Br J Pharmacol. 1986 Feb;87(2):345–355. doi: 10.1111/j.1476-5381.1986.tb10823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Henderson G., Johnson J. W., Ascher P. Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor. J Physiol. 1990 Nov;430:189–212. doi: 10.1113/jphysiol.1990.sp018288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Honoré T., Davies S. N., Drejer J., Fletcher E. J., Jacobsen P., Lodge D., Nielsen F. E. Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science. 1988 Aug 5;241(4866):701–703. doi: 10.1126/science.2899909. [DOI] [PubMed] [Google Scholar]
  5. Huettner J. E. Glutamate receptor channels in rat DRG neurons: activation by kainate and quisqualate and blockade of desensitization by Con A. Neuron. 1990 Sep;5(3):255–266. doi: 10.1016/0896-6273(90)90163-a. [DOI] [PubMed] [Google Scholar]
  6. Ishida M., Shinozaki H. Novel kainate derivatives: potent depolarizing actions on spinal motoneurones and dorsal root fibres in newborn rats. Br J Pharmacol. 1991 Dec;104(4):873–878. doi: 10.1111/j.1476-5381.1991.tb12520.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lodge D., Jones M. G., Palmer A. J. Excitatory amino acids: new tools for old stories or pharmacological subtypes of glutamate receptors: electrophysiological studies. Can J Physiol Pharmacol. 1991 Jul;69(7):1123–1128. doi: 10.1139/y91-164. [DOI] [PubMed] [Google Scholar]
  9. Long S. K., Evans R. H., Krijzer F. Effects of depressant amino acids and antagonists on an in vitro spinal cord preparation from the adult rat. Neuropharmacology. 1989 Jul;28(7):683–688. doi: 10.1016/0028-3908(89)90151-2. [DOI] [PubMed] [Google Scholar]
  10. Long S. K., Smith D. A., Siarey R. J., Evans R. H. Effect of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX) on dorsal root-, NMDA-, kainate- and quisqualate-mediated depolarization of rat motoneurones in vitro. Br J Pharmacol. 1990 Aug;100(4):850–854. doi: 10.1111/j.1476-5381.1990.tb14103.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lovinger D. M., Weight F. F. Glutamate induces a depolarization of adult rat dorsal root ganglion neurons that is mediated predominantly by NMDA receptors. Neurosci Lett. 1988 Dec 5;94(3):314–320. doi: 10.1016/0304-3940(88)90037-7. [DOI] [PubMed] [Google Scholar]
  12. Mayer M. L., Vyklicky L., Jr Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1411–1415. doi: 10.1073/pnas.86.4.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sheardown M. J., Nielsen E. O., Hansen A. J., Jacobsen P., Honoré T. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia. Science. 1990 Feb 2;247(4942):571–574. doi: 10.1126/science.2154034. [DOI] [PubMed] [Google Scholar]
  14. Simmonds M. A. Depolarizing responses to glycine, beta-alanine and muscimol in isolated optic nerve and cuneate nucleus. Br J Pharmacol. 1983 Jul;79(3):799–806. doi: 10.1111/j.1476-5381.1983.tb10018.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Thomson A. M. Glycine is a coagonist at the NMDA receptor/channel complex. Prog Neurobiol. 1990;35(1):53–74. doi: 10.1016/0301-0082(90)90040-n. [DOI] [PubMed] [Google Scholar]
  16. Tse F. W., Weiss S., MacVicar B. A. Quisqualate agonists occlude kainate-induced current in cultured striatal neurons. Neuroscience. 1991;43(2-3):429–436. doi: 10.1016/0306-4522(91)90305-8. [DOI] [PubMed] [Google Scholar]
  17. Watkins J. C., Pook P. C., Sunter D. C., Davies J., Honore T. Experiments with kainate and quisqualate agonists and antagonists in relation to the sub-classification of 'non-NMDA' receptors. Adv Exp Med Biol. 1990;268:49–55. doi: 10.1007/978-1-4684-5769-8_6. [DOI] [PubMed] [Google Scholar]

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

RESOURCES