Putative Transmitters

  • David Ottoson
Chapter

Abstract

It is now generally agreed that most neurons in the central nervous system communicate with one another by releasing chemical transmitters. Despite arduous efforts, only a few compounds have been identified which can with various degrees of certainty be considered as neurotransmitters. To be identified as a transmitter, a substance should fulfil certain criteria. The main properties to be established are the presence of the substance in the presynaptic terminals and its release during presynaptic activity. Furthermore, there should be a correlation between its release and the amount of presynaptic activity; local administration of the compound should produce the same effect as presynaptic activity and substances antagonistic to the putative transmitter should block synaptic transmission. Actually, none of the compounds generally considered to be transmitters in the central nervous system fulfils all these criteria. Because of the complexity of the central nervous system, it is technically difficult to prove the release of a putative transmitter or to administer it locally at the synapse. The rigorous criteria which are applied to the peripheral system therefore cannot be easily satisfied within the central nervous system.

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Bibliography

Suggested Reading and Reviews

  1. Bennett, M. V. L. (1972). A comparison of electrically and chemically mediated transmission, in Structure and Function of Synapses, eds G. D. Pappas and D. P. Purpura, Raven Press, New York, pp. 221–256Google Scholar
  2. Bennett, M. V. L. (ed.) (1974). Synaptic Transmission and Neuronal Interaction, Raven Press, New YorkGoogle Scholar
  3. Bloom, F. E. (1975). Central noradrenergic synaptic mechanisms, in The Nervous System, vol. 1, ed. D. B. Tower, Raven Press, New York, pp. 373–380Google Scholar
  4. Bodian, D. (1972). Synaptic diversity and characterization by electron microscopy, in Structure and Function of Synapses, eds G. D. Pappas and D. P. Purpura, Raven Press, New York, pp. 45–65Google Scholar
  5. Brownstein, M. (1977). Biological active peptides in the mammalian central nervous system, in Peptides in Neurobiology, ed. H. Gainer, Plenum Press, New York, pp. 145–170CrossRefGoogle Scholar
  6. Costa, E. and Trabucchi, M. (eds) (1978). The Endorphins, Advances in Biochemical Psychopharmacology, vol. 18, Raven Press, New YorkGoogle Scholar
  7. Dahlstrom, A. (1969). Fluorescence histochemistry of monoamines in the CNS, in Basic Mechanisms of the Epilepsies, eds H. H. Jasper, A. A. Ward and A. Pope, Little, Brown and Co.Google Scholar
  8. Boston Eccles, J. C. (1961). The mechanism of synaptic transmission, Ergebn. Physiol., 51, 299–430CrossRefGoogle Scholar
  9. Eccles, J. C. (1963). Presynaptic and postsynaptic inhibitory actions in the spinal cord, in Brain Mechanisms, ed. G. Moruzzi, Elsevier, AmsterdamGoogle Scholar
  10. Eccles, J. C. (1964). The Physiology of Synapses, Springer-Verlag, BerlinCrossRefGoogle Scholar
  11. Eccles, J. C. (1967). Postsynaptic inhibition in the central nervous system, in The Neurosciences. A Study Program, eds. G. C. Quarton, T. Mel- nechuk and F. O. Schmitt, Rockefeller University Press, New York, pp. 408–427 Gainer, H., Loh, Y. P. and Same, Y. (1977). Biosynthesis of neuronal peptides, in Peptides in Neurobiology, ed. H. Gainer, Plenum Press, New York, pp. 183–219 Grundfest, H. (1957). Electrical inexcitability of synapses and some consequences in the central nervous system, Physiol Rev., 37, 337–361 Grundfest, H. (1967). Synaptic and ephaptic transmission, in The Neurosciences. A Study Program, eds G. C. Quarton, T. Melnechuk and F. O. Schmitt, Rockefeller University Press, New York, pp. 353–372Google Scholar
  12. Hall, Z. W., Hildebrand, J. G. and Kravitz, E. A. (1972). Chemistry of Synaptic Transmission, Chiron Press, NewtonGoogle Scholar
  13. Hökfelt, T. (1971). Ultrastructural localization of intraneuronal monoamines. Some aspects of methodology, in Histochemistry of Nervous Transmission, Progress in Brain Research, ed. O. Eränkö, Elsevier, Amsterdam, pp. 213–222Google Scholar
  14. Hökfelt, T., Johansson, O., Kellerth, J.-O., Ljung- dahl, Ä., Nilsson, G., Nygards, A. and Pernow, B. (1976). Immunohistochemical distribution of substance P, in Substance P, eds U. S. von Euler and B. Pernow, Raven Press, New York, pp. 117–145Google Scholar
  15. Hornykiewicz, O. (1973). Dopamine in the basal ganglia: Its role and therapeutic implications (including the clinical use of LDOPA), Br. Med. Bull., 29, 172–178 Iversen, L L. (1970). Neurotransmitters, neurohormones and other small molecules in neurons, in The Neurosciences. Second Study Program, ed. F. O. Schmitt, Rockefeller University Press, New York, pp. 768–781Google Scholar
  16. Iversen, L. L (1975). Dopamine receptors in the brain, Science, 188, 1084–1089PubMedCrossRefGoogle Scholar
  17. Iversen, L. L (1979). The chemistry of the brain, Scient. Am., 241, 118–129CrossRefGoogle Scholar
  18. Jones, D. G. (1975). Synapses and Synaptosomes. Morphological Aspects, Chapman and Hall, LondonGoogle Scholar
  19. Kandel, E. R. (1979). Small systems of neurons, Scient. Am., 241, 61–70CrossRefGoogle Scholar
  20. Kosterlitz, H. W. and McKnight, A. T. (1981). Opioid peptides and sensory function, in Progress in Sensory Physiology, vol. 1, ed. D. Ottoson, Springer-Verlag, Heidelberg, pp. 32–95Google Scholar
  21. McLennan, H. (1970). Synaptic Transmission, W. B. Saunders, PhiladelphiaGoogle Scholar
  22. Nicoli, R. A. (1975). Peptide receptors in CNS, in Handbook of Psychopharmacology, vol. 4, eds L. L. Iversen, S. D. Iversen and S. H. Snyder, Plenum Press, New York, pp. 229–263Google Scholar
  23. Otsuka, M. and Takahashi, T. (1977). Putative peptide neurotransmitters, Ann. Rev. Pharmacol. Toxicol 17, 425–439CrossRefGoogle Scholar
  24. Pappas, G. D. (1975). Ultrastructural basis of synaptic transmission, in The Nervous System, vol. 1, ed. D. B. Tower, Raven Press, New York, pp. 19–30Google Scholar
  25. Pappas, G. D. and Purpura, D. P. (1972). Structure and Function of Synapses, Raven Press, New YorkGoogle Scholar
  26. Pappas, G. D. and Waxman, S. G. (1972). Synaptic fine structure — morphological correlates of chemical and electrotonic transmission, in Structure and Function of Synapses, eds G. D. Pappas and D. P. Purpura, Raven Press, New York, pp. 1–43Google Scholar
  27. Peters, A. (1968). The morphology of axons of the central nervous system, in The Structure and Function of Nervous Tissue, vol. 1, ed. G. H. Bourne, Academic Press, New York, pp. 141–186Google Scholar
  28. Pfenninger, K. H. (1973). Synaptic morphology and cytochemistry, Prog. Histochem. Cyto- chem., 5(1), 1–86Google Scholar
  29. Pfenninger, K. H. (1979). Synaptic-membrane differentiation, in The Neurosciences. Fourth Study Program, eds. F. O. Schmitt and F. G. Worden, MIT Press, Cambridge, MA, pp. 779–795Google Scholar
  30. Phillis, J. W. (1966). The Pharmacology of Synapses, Pergamon Press, OxfordGoogle Scholar
  31. Schmidt, R. F. (1971). Presynaptic inhibition in the vertebrate central nervous system, Ergebn. Physiol, 63, 21–108Google Scholar
  32. Shapiro, E., Klein, M. and Kandel, E. (1981). Ionic mechanisms and behavioral functions of presynaptic facilitation and presynaptic inhibition in Aplysia: A model system for studying the modulation of signal transmission in sensory neurons, in Progress in Sensory Physiology, vol. 1, eds H. Autrum, D. Ottoson, E. R. Perl and R. F. Schmidt, Springer-Verlag, Heidelberg, pp. 97–137CrossRefGoogle Scholar
  33. Snyder, S. H. and Bennett, J. P., Jr (1976). Neurotransmitter receptors in the brain: biochemical identification, Ann Rev. Physiol, 38, 153–175CrossRefGoogle Scholar
  34. Triggle, D. J. and Triggle, C. R. (1976). Chemical Pharmacology of the Synapse, Academic Press, New YorkGoogle Scholar
  35. Ungerstedt, U. (1974). Brain dopamine neurones and behavior, in The Neurosciences. Third Study Program, eds. F. O. Schmitt and F. G. Worden, MIT Press, Cambridge, MA, pp. 695–703Google Scholar
  36. Vale, W. and Brown, M. (1979). Neurobiology of peptides, in The Neurosciences. Fourth Study Program, eds F. O. Schmitt and F. G. Worden, MIT Press, Cambridge, MA, pp. 1027–1041Google Scholar

Original Papers

  1. Bennett, M. V. L., Nakajima, Y. and Pappas, G. D. (1967). Physiology and ultrastructure of electrotonic junctions, I. Supramedullary neurons, J. Neurophysiol., 30, 161–179PubMedGoogle Scholar
  2. Bodian, D. (1966). Synaptic types on spinal motoneurons: an electron microscopic study, Bull Johns Hopkins Hosp., 119, 16–45Google Scholar
  3. Burke, R. E. (1967). Composite nature of the monosynaptic excitatory postsynaptic potential, J. Neurophysiol., 30, 1114–1137PubMedGoogle Scholar
  4. Conradi, S. (1909). On motoneuron synaptology in adult cats, Acta Physiol Scand., Suppl 332, 1–115Google Scholar
  5. Curtis, D. R. (1959). Pharmacological investigations upon inhibition of spinal neurones, J. Physiol. (Lond.), 145, 175–192CrossRefGoogle Scholar
  6. Curtis, D. R., Duggan, A. W., Felix, D. and Johnston, G. A. R. (1970). GABA, bicuculline and central inhibition, Nature, 226, 1222–1224PubMedCrossRefGoogle Scholar
  7. Curtis, D. R. and Eccles, R. M. (1958). The excitation of Renshaw cells by pharmacological agents applied electrophoretically, J. Physiol (Lond.), 141, 435–445CrossRefGoogle Scholar
  8. Curtis, D. R. and Eccles, J. C. (1959). The time courses of excitatory and inhibitory synaptic actions, J. Physiol (Lond.), 145, 520–546Google Scholar
  9. Curtis, D. R. and Eccles, J. C. (1960). Synaptic action during and after repetitive stimulation, J. Physiol (Lond.), 150, 374–398CrossRefGoogle Scholar
  10. Curtis, D. R., Lodge, D. and Brand, S. J. (1977). GABA and spinal afferent terminal excitability in the cat, Brain Res., 130, 360–363PubMedCrossRefGoogle Scholar
  11. Curtis, D. R. and Ryall, R. W. (1966). The synaptic excitations of Renshaw cells, Exp. Brain Res., 2, 81–96PubMedGoogle Scholar
  12. Dale, H. H. (1935). Pharmacology and nerve-endings, Proc. R. Soc. B, 28, 319–322Google Scholar
  13. Eccles, J. C. (1949). A review and restatement of the electrical hypothesis of synaptic excitatory and inhibitory action, Arch. Sci Physiol., 3, 567–584Google Scholar
  14. Eccles, J. C., Eccles, R. M. and Lundberg, A. (1957). Synaptic actions on motoneurones in relation to the two components of the group I muscle afferent volley, J. Physiol. (Lond.), 136, 527–546PubMedCentralCrossRefGoogle Scholar
  15. Eccles, J. C., Eccles, R. M. and Magni, F. (1961). Central inhibitory action attributable to presynaptic depolarization produced by muscle afferent volleys, J. Physiol (Lond.), 159, 147–166CrossRefGoogle Scholar
  16. Eccles, J. C., Schmidt, R. F. and Willis, W. D. (1963). Pharmacological studies on presynaptic inhibition, J Physiol (Lond.), 168, 500–530CrossRefGoogle Scholar
  17. Eccles, J. C., Schmidt, R. F. and Willis, W. D. (1963). The mode of operation of the synaptic mechanism producing presynaptic inhibition, J. Neurophysiol, 26, 523–536Google Scholar
  18. Eccles, R. M., Shealy, C. N. and Willis, W. D. (1963). Patterns of innervation of kitten motoneurones, J. Physiol (Lond.), 165, 392–402CrossRefGoogle Scholar
  19. Henneman, E., Somjen, G. and Carpenter, D. O. (1965). Functional significance of cell size in spinal motoneurons, J. Neurophysiol., 28, 560–580PubMedGoogle Scholar
  20. Henneman, E., Somjen, G., and Carpenter, D. O. (1965). Excitability and inhibitibility of motoneurons of different sizes, J. Neurophysiol., 28, 599–620PubMedGoogle Scholar
  21. Hökfelt, T. (1967). On the ultrastructural localization of noradrenaline in the central nervous system of the rat, Z. Zellforsch., 79, 110–117PubMedCrossRefGoogle Scholar
  22. Hokfelt, T., Johansson, O., Fuxe, K., Goldstein, M. and Park, D. (1976). Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon, Med. Biol, 54, 427–453PubMedGoogle Scholar
  23. Jankowska, E. and Roberts, W. J. (1972). Synaptic actions of single interneurons mediating reciprocal la inhibition of motoneurons, J. Physiol. (Lond.), 222, 623–642PubMedCentralCrossRefGoogle Scholar
  24. Kravitz, E. A. (1967). Acetylcholine, γ-aminobutyric acid and glutamic acid: physiological and chemical studies related to their roles as neurotransmitter agents, in The Neurosciences. A Third Study Program, eds G. C. Quarton, T. Melnechuk and F. O. Schmitt, Rockefeller University Press, New York, pp. 433–444Google Scholar
  25. Otsuka, M. and Konishi, S. (1976). Substance P and excitatory transmitter of primary sensory neurons, Cold Spring Harbour Symp. Quant. Biol., 40, 135–144CrossRefGoogle Scholar

Copyright information

© D. Ottoson 1983

Authors and Affiliations

  • David Ottoson
    • 1
  1. 1.Department of Physiology IIKarolinska InstitutetStockholmSweden

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