Summary
Kainic acid (a rigid conformational analogue of glutamate), N-methyl-d-aspartate (the methylated derivative of aspartate), and (-)-nuciferine (an aporphine alkaloid with a depressant effect on glutamate-induced neuronal firing), which, so far, have been examined in microiontophoretic studies, were investigated in spinal cats for their effects on some spinal cord activities after intravenous injections.
At low doses, kainic acid (0.3 mg kg−1) enhanced segmental monosynaptic but not polysynaptic ventral root reflexes and increased the excitability of motoneurones, whereas N-methyl-d-aspartate (3 mg kg−1) facilitated polysynaptic but not monosynaptic reflexes. Higher doses of the two amino acids depolarized motoneurones and primary afferent endings, enhanced monosynaptic reflexes and depressed polysynaptic reflexes.
(-)-Nuciferine (1–10 mg kg−1) depressed monosynaptic but not polysynaptic ventral root reflexes in a dose-dependent manner and antagonized the effects of kainic acid but not of N-methyl-d-aspartate on the spinal cord.
The results are consistent with the hypothetical excitatory transmitter role of glutamate in primary afferents and of aspartate in excitatory spinal cord interneurones; the findings also suggest that (-)-nuciferine may be used as a systemically effective, rather selective blocker of central glutamate receptors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ben-Ari, Y., Kelly, J. S.: Specificity of nuciferine as an antagonist of amino acid and synaptically evoked activity in the cells of the feline thalamus. J. Physiol. (Lond.) 251, 25–27 P (1975)
Biscoe, T. J., Evans, R. H., Headley, P. M., Martin, M. R., Watkins, J. C.: Structure-activity relations of excitatory amino acids on frog and rat spinal neurones. Br. J. Pharmacol. 58, 373–382 (1976)
Curtis, D. R., Lodge, D., Brand, S. J.: GABA and spinal afferent terminal excitability in the cat. Brain Res. 130, 360–363 (1977)
Davidoff, R. A., Graham, L. T., Jr., Shank, R. P., Werman, R., Aprison, M. H.: Changes in amino acid concentrations associated with loss of spinal interneurons. J. Neurochem. 14, 1025–1031 (1967)
Graham, L. T., Jr., Shank, R. P., Werman, R., Aprison, M. H.: Distribution of some synaptic transmitter suspects in cat spinal cord: glutamic acid, aspartic acid, γ-aminobutyric acid, glycine and glutamine. J. Neurochem. 14, 465–472 (1967)
Hamon, M., Bourgoin, S., Enjalbert, A., Bockaert, J., Hery, F., Ternaux, J. P., Glowinski, J.: The effects of quipazine on 5-HT metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 99–108 (1976)
Hind, J. M., Kelly, J. S.: The blockade of synaptic and amino acid evoked firing in the cuneate nucleus by the glutamic acid antagonist nuciferine (1-5,6-dimethoxyaporphine). J. Physiol. (Lond.) 246, 97–98 P (1975)
Iles, J. F.: Central terminations of muscle afferents on motoneurones in the cat spinal cord. J. Physiol. (Lond.) 262, 91–117 (1976)
Jacoby, J. H., Howd, R. A., Levin, M. S., Wurtman, R. J.: Mechanisms by which quipazine, a putative serotonin receptor agonist, alters brain 5-hydroxyindole metabolism. Neuropharmacology 15, 529–534 (1976)
McCulloch, R. M., Johnston, G. A. R., Game, C. J. A., Curtis, D. R.: The differential sensitivity of spinal interneurones and Renshaw cells to kainate and N-methyl-d-aspartate. Exp. Brain Res. 21, 515–518 (1974)
Macko, E., Douglas, B., Weisbach, J. A., Waltz, D. T.: Studies on the pharmacology of nuciferine and related aporphines. Arch. Int. Pharmacodyn. 197, 261–273 (1972)
Polc, P., Möhler, H., Haefely, W.: The effect of diazepam on spinal cord activities: possible sites and mechanisms of action. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 319–337 (1974)
Ruch-Monachon, M. A., Jalfre, M., Haefely, W.: Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine. Arch. Int. Pharmacodyn. 219, 269–286 (1976)
Simon, J. R., Contrera, J. F., Kuhar, M. J.: Binding of [3H]kainic acid, an analogue of l-glutamate, to brain membranes. J. Neurochem. 26, 141–147 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Polc, P., Haefely, W. Effects of intravenous kainic acid, N-methyl-d-aspartate, and (-)-nuciferine on the cat spinal cord. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 199–203 (1977). https://doi.org/10.1007/BF00500961
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00500961