Interactions of Coexisting Neurotransmitters and Effects of Chronic Drug Treatment

  • Tamas Bartfai
  • Kerstin Iverfeldt
  • Peter Serfözö
  • Sven-Ove Ögren
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)


The phenomenon of coexistence of classical neurotransmitters and neuroactive peptides has been demonstrated in a number of cases in the central and peripheral nervous system (cf. Hökfelt et al., 1980; Cuello, 1982; Lundberg and Hökfelt, 1983). In the descending bulbospinal pathway originating from the raphe nuclei, coexistence of at least three putative neurotransmitters; the undecapeptide substance P (SP), the tripeptide thyrotropinreleasing hormone (TRH) and serotonin (5-hydroxytryptamine, 5-HT) has been shown using immunohistochemical methods (Chan-Palay et al., 1978; Hökfelt et al., 1978; Johansson et al., 1981). Treatment with the serotonergic “neurotoxins” 5,6- or 5,7-dihydroxytryptamine results in an almost complete loss of 5-HT, TRH and SP immunoreactive fibers in the ventral spinal cord (Björklund et al., 1979; Johansson et al., 1981; Gilbert et al., 1982; Marsden et al., 1982) although findings suggesting a limited scope of coexistence only, were also reported (Towle et al., 1986).


Spinal Cord Lumbar Spinal Cord Tachykinin Receptor Classical Neurotransmitter Ventral Spinal Cord 
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  1. Agnati, L.F., Fuxe, K., Benfenati, F., Zini, I. and Hökfelt, T. (1983) On the functional role of coexistence of 5-HT and substance P in bulbospinal 5-HT neurons. Substance P reduces affinity and increases density of 3H-5-HT binding sites. Acta Physiol. Scand., 117, 299–301.CrossRefGoogle Scholar
  2. Barbeau, H. and Bédard, P. (1981) Similar motor effects of 5-HT and TRH in rats following chronic spinal transection and 5,7-dihydroxytryptamine injection. Neuropharmacol., 20, 477–481.CrossRefGoogle Scholar
  3. Björklund, A.J., Emson, P.C., Gilberg, R.F.T. and Shagerberg, G. (1979) Further evidence for the possible coexistence of 5-hydroxytryptamine and substance P in medullary raphe neurons of the rat brain. Br. J. Pharmacol., 66, 112P - 113 P.Google Scholar
  4. Brodin, E., Peterson, L.-L., Ogren, S.-O. and Bartfai, T. (1984) Chronic treatment with serotonin uptake inhibitor zimelidine elevates substance P levels in rat spinal cord. Acta Physiol. Scand., 122, 209–211.Google Scholar
  5. Bury, R.W. and Mashford, M.L. (1976) Biological activity of C-terminal partial sequences of substance P. J. Med. Chem., 19, 854–858.CrossRefGoogle Scholar
  6. Cerrito, F. and Raiteri, M. (1979) Serotonin release is modulated by presynaptic autoreceptors. Eur. J. Pharmacol., 57, 427–430.CrossRefGoogle Scholar
  7. Chan-Palay, V., Jonsson, G. and Palay, S.L. (1978) Serotonin and substance P coexist in neurons of the rat’s central nervous system. Proc. Natl. Acad. Sci., 75, 1582–1586.CrossRefGoogle Scholar
  8. Cuello, A.C. (1982) Cotransmission. MacMillan Press, London.Google Scholar
  9. Gilbert, R.F.T., Emson, P.C., Hunt, S.P., Bennet, G.W., Marsden, C.A., Sandberg, B.E.B., Steinbusch, H.W.M. and Verhofstad, A.A.J. (1982) The effects of monoamine neurotoxins on peptides in the rat spinal cord. Neuroscience, 7, 69–78.CrossRefGoogle Scholar
  10. Göthert, M. (1980) Serotonin-receptor-mediated modulation of Ca2+ dependent 5-hydroxytryptamine release from neurons of the rat brain cortex. Naunyn-Schmiedeberg’s Arch. Pharmacol., 314, 223–230.Google Scholar
  11. Hökfelt, T., Ljungdahl, A., Steinbuch, H., Verhofstad, A., Nilsson, G., Brodin, E., Pernow, B. and Goldstein, M. (1978) Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system. Neuroscience, 3, 517–538.CrossRefGoogle Scholar
  12. Hökfelt, T., Johansson, O., Ljungdahl, A., Lundberg, A., Lundberg, J.M. and Schultzberg, M. (1980) Peptidergic neurons. Nature, 284, 515–521.CrossRefGoogle Scholar
  13. Iverfeldt, K., Peterson, L.-L., Brodin, E., Ogren, S.-O. and Bartfai, T. (1986) Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment. Naunyn-Schmiedeberg’s Arch. Pharmacol., 333, 1–6.Google Scholar
  14. Johansson, O., Hökfelt, T., Pernow, B., Jeffcoate, S.L., White, N., Steinbusch, H.W.M., Verhofstad, A.A.J., Emson, P.C. and Spindel, E. (1981) Immunohistochemical support for three putative transmitters in one neuron: coexistence of 5-hydroxytryptamine, substance P and thyrotropin releasing hormone-like immunoreactivity in medullary neurons projecting to the spinal cord. Neuroscience, 6, 1857–1881.CrossRefGoogle Scholar
  15. Konishi, S. and Otsuka, M. (1974) Excitatory action of hypothalamic substance P on spinal motoneurons of newborn rats. Nature, 252, 734–735.CrossRefGoogle Scholar
  16. Lechan, R.M., Wu, P., Jackson, M.D., Wolf, H., Cooperman, S., Mandel, G. and Goodman, R.H. (1986) Thyrotropin-releasing hormone precursor: Characterization in rat brain. Science, 231, 159–161.CrossRefGoogle Scholar
  17. Lighton, C., Bennett, G.W. and Marsden, C.A. (1985) Increase in levels and ex vivo release of thyrotropin-releasing hormone (TRH) in specific regions of the CNS of the rat by chronic treatment with antidepressants. Neuropharmacol., 24, 401–406.CrossRefGoogle Scholar
  18. Lundberg, J.M. and Hökfelt, T. (1983) Coexistence of peptides and classical neurotransmitters. Trends in Neurosci., 6, 325–333.CrossRefGoogle Scholar
  19. Marsden, C.A., Bennett, G.W., Irons, J., Gilbert, R.F.T. and Emson, P.C. (1982) Localization and release of 5-hydroxytryptamine, thyrotropin releasing hormone and substance P in rat ventral spinal cord. Comp. Biochem. Physiol., 72C, 263–270.CrossRefGoogle Scholar
  20. McKelvy, J.F. (1982) Biosynthesis of thyrotropin releasing hormone. Front. Horm. Res., 10, 73–84.Google Scholar
  21. Mitchell, R. and Fleetwood-Walker, S. (1981) Substance P, but not TRH modulates the 5-HT autoreceptor in ventral lumbar spinal cord. Eur. J. Pharmacol., 76, 119–120.CrossRefGoogle Scholar
  22. Monroe, P.J. and Smith, D.J. (1985) Demonstration of an auto-receptor rodulating the release of [3H]5-hydroxytryptamine from a synaptosomal-rich spinal cord tissue preparation. J. Neurochem., 45, 1886–1894.CrossRefGoogle Scholar
  23. Nawa, H., Hirose, T., Takashima, H., Inayama, S. and Nakanishi, S. (1983) Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature (Lond.), 306, 32–36.CrossRefGoogle Scholar
  24. Otsuka, M. and Konishi, S. (1976) Substance P and excitatory transmitter of primary sensory neurons. Cold Spring Harb. Symp. Quant. Biol., 40, 135–143.CrossRefGoogle Scholar
  25. Ouafik, L.H., Dutour, A., Castanas, E., Boudouresque, F. and Oliver, C. (1985) Evidence for a precursor for TRH in the neonatal rat pancreas. Biochem. Biophys. Res. Commun., 128, 664–669.CrossRefGoogle Scholar
  26. Richter, K., Kawashima, E., Egger, R. and Kreil, G. (1984) Biosynthesis of thyrotropin releasing hormone in the skin of Xenopus laevis: partial sequence of the precursor deduced from cloned cDNA. EMBO J., 3, 617–621.Google Scholar
  27. Solti, M. and Bartfai, T. (1987) Tachykinin regulation of serotonin release: enhancement of [3H]serotonin release from rat cerebral cortex by neuromedin K and substance P acting at distinct receptor sites. Brain Res., in press.Google Scholar
  28. Stauderman, K.A. and Jones, D.J. (1986) Presynaptic serotonin receptors regulate [3H]serotonin release from rat spinal cord synaptosomes. Eur. J. Pharmacol., 120, 107–109.CrossRefGoogle Scholar
  29. Towle, A.C., Breese, G.R., Mueller, R.A., Hunt, R. and Lauder, J.M. (1986) Early postnatal administration of 5,7-dihydroxytryptamine: Effects on substance P and thyrotropinreleasing hormone neurons and terminals in rat brain. Brain Res., 363, 38–46.CrossRefGoogle Scholar
  30. Tremblay, L.E., Maheux, R. and Bédard, P.J. (1986) Substance P in the lumbar spinal cord of the rat affects the motor response to 5-HTP and TRH. Neuropharmacol., 25, 419–424.CrossRefGoogle Scholar
  31. Tsai, H.-Y., Maeda, S., Iwatsubo, K. and Inoki, R. (1984) Effect of neuroactive peptides on labeled 5-hydroxytryptamine release from rat spinal cord in vitro. Jpn. J. Pharmacol., 35, 403–406.CrossRefGoogle Scholar
  32. White, S.R. (1985) A comparison of the effects of serotonin, substance P and thyrotropin-releasing hormone on excitability of rat spinal motoneurons in vivo. Brain Res., 335, 63–70.CrossRefGoogle Scholar

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© The Wenner-Gren Center 1987

Authors and Affiliations

  • Tamas Bartfai
  • Kerstin Iverfeldt
  • Peter Serfözö
  • Sven-Ove Ögren

There are no affiliations available

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