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Reflections on Substance P and Some Related Peptides

  • T. Hökfelt
  • G. Ju
Conference paper

Abstract

In contrast to many other peptides, substance P was right away purified both from intestine and brain. This may be regarded as a sign of the remarkable intuition that characterized Ulf von Euler’s research throughout his career. In this way substance P never belonged to the many gastrointestinal peptides which to our surprise later on also were discovered in the brain. The research which followed the original discovery of substance P by von Euler and Gaddum (15) has exhibited a wavy pattern with bursts of activity appearing at shorter and shorter intervals, as schematically indicated in Figure 1. Thus, substance P research was slow after the initial studies until the 50’ s, when several groups initiated new efforts, including researchers such as Lembeck, Pernow, Umrath and Zetler, resulting i.a. in an extensive mapping of distribution of substance P activity in various tissues (12) as well as the suggestion that substance P could act as transmitter substance in primary sensory neurons (9). Although interest in substance P remained in the following years, no dramatic events occurred until the beginning of the 70’ s, when Susan Leeman and her collaborators sequenced substance P and showed that it represents a peptide consisting of eleven amino acids. Subsequently this group synthesized substance P, raised antisera and worked out a radioimmunoassay (RIA). This major progress led to intense activity in many laboratories allover the world. The work in Masanori Otsuka’s laboratory was seminal in defining a functional role for substance P and, for example, at the Karolinska Institute Bengt Pernow initiated a new wave of substance P research. In the following years the distribution of substance P was outlined both with radioimmunoassay and immunohistochemistry, and novel aspects of the function of substance P were outlined. We remember particularly Jim Henry’s work on a possible involvement of substance P in pain transmission, and the elucidation by Fred Lembeck and his associates of the role of substance P in the axon reflex.

Keywords

Dorsal Root Ganglion Primary Sensory Neuron Calcitonin Gene Capsaicin Treatment Eleven Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Amara SG, Arriza JL, Leff SE, Swanson LW, Evans RM, Rosenfeld MG (1985) Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin generelated peptide. Science 229: 1094-1097.PubMedCrossRefGoogle Scholar
  2. 2.
    Bergstrom L, Torrens Y, Saffroy M, Beaujouan JC, Lavielle S, Chassaing G, Morgat JL, Glowinski J, Marquet A (1986) ((3H)-NKB) and (125I)-bolton hunter eledoisin ((125I)-BHE) label identical tachykinin binding sites in the rat brain. In: Substance P and Neurokinins (J. Henry, ed) Springer-Verlag, New York, in press.Google Scholar
  3. 3.
    Dalsgaard CJ, Vincent SR, Hokfelt T, Lundberg JM, Dahlstrom A, Schultzberg M, Dockray GJ, Cuello AC (1982) Coexistence of cholecystokinin- and substance P-like peptides in neurons of the dorsal root ganglia of the rat. Neurosci Lett 33: 159-163.PubMedCrossRefGoogle Scholar
  4. 4.
    Gibson SJ, P~lak JM, Bloom SR, Sabate JM, Mulderry PM, Ghatei MA, Morrison JFB, Kelly JS, Rosenfeld MG (1984) Calcitonin generelated peptide (CGRP)-immunoreactivity in the spinal cord of man and of eight species. J Neurosci 4: 3101-3111.PubMedGoogle Scholar
  5. 5.
    Ju G, Hokfelt T, Brodin E, Fahrenkrug J, Fischer JA, Frey P, Elde RP, Brown R (1986a) Calcitonin gene-related peptide (CGRP)immunoreactive primary sensory neurons in rat and their relation to substance P-,somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells. Cell Tiss Res, in press.Google Scholar
  6. 6.
    Ju G, Hokfelt T, Fischer JA, Frey P, Rehfeld JF, Dockray GJ (1986b) Does cholecystokininlike immunoreactivity in primary sensory neurons represent calcitonin gene related peptide? Neurosci Letts, in press.Google Scholar
  7. 7.
    Kruger L, Sternini C, Mantyh CR, Mantyh PW, Brecha NC, Silverman JD, Colin S, Yeh Y (1986) Calcitonin gene-related peptide (CGRP) immunoreactivity and receptor binding sites in relation to specific sensory pathways in the rat. In: Proc. IUPS, Vol 16, p 328.Google Scholar
  8. 8.
    Le Greves P, Nyberg F, Terenius L, Hokfelt T (1985) Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. Eur J Pharmacol 115: 309-311.PubMedCrossRefGoogle Scholar
  9. 9.
    Lembeck F (1953) Zur Frage der zentralen Ubertragung afferenter Impulse. III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsal en Wurzeln des Rückenmarks. Naunyn-Schmiedeberg’s Arch Exp Pathol Pharmakol 219: 197-213.Google Scholar
  10. 10.
    Marley PD, Nagy JI, Emson PC, Rehfeld JF (1982) Cholecystokinin in the rat spinal cord: distribution and lack of effect of neonatal capsaicin treatment and rhizotomy. Brain Res 238: 494-498.PubMedCrossRefGoogle Scholar
  11. 11.
    O’Donohue TL, Helke CJ, Burcher E, Shults CW, Buch SH (1986) Autoradiographic distribution of binding sites for iodinated tachykinins in the rat CNS. In: Substance P and Neurokinins (J. Henry, ed) Springer-Verlag, New York, in press.Google Scholar
  12. 12.
    Pernow B (1953) Studies on substance P. Purification, occurrence and biological actions. Acta Physiol Scand 105 (Suppl) 29: 1-90.Google Scholar
  13. 13.
    Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RH (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue specific RNA processing. Nature (London) 304: 129-135.CrossRefGoogle Scholar
  14. 14.
    Schultzberg M, Dockray GJ, Williams RG (1982) Capsaicin depletes CCK-like immunoreactivity detected by immunohistochemistry, but not that measured by radioimmunoassay in rat dorsal spinal cord. Brain Res 235: 198-204.PubMedCrossRefGoogle Scholar
  15. 15.
    Von Euler US, Gaddum JH (1931) An unidentified depressor substance in certain tissue extracts. J Physiol (London) 72: 74-87.Google Scholar
  16. 16.
    Wiesenfeld-Hallin Z, Hökfelt T, Lundberg JM, Forssmann WG, Reinecke M, Tschopp FA, Fischer JA (1984) Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Lett 52: 199-204.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1987

Authors and Affiliations

  • T. Hökfelt
    • 1
  • G. Ju
    • 1
  1. 1.Department of HistologyKarolinska InstitutetStockholmSweden

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