Evidence that axons containing substance P in the guinea-pig ileum are of intrinsic origin

  • R. Franco
  • M. Costa
  • J. B. Furness


Acid extracts from both normal and extrinsically denervated ileum contained a compound which was indistinguishable from synthetic substance P; this compound was assayed by examining its contractile effect on the longitudinal muscle of segments of ileum in which receptors for acetylcholine and histamine were blocked. Contractions caused by the compound were markedly and selectively antagonized when the ileum was made insensitive to the action of substance P. The activities in the extract and of synthetic substance P were both destroyed by chymotrypsin but were not affected by trypsin or carboxypeptidase B. The concentrations of substance P-like material in normal and extrinsically denervated segments were not significantly different, being equivalent to 0.48 μg of substance P per g of external muscle plus myenteric plexus. A compound with substance P-like activity was liberated by stimulation of intramural nerves, either electrically or by dimethylphenylpiperazinium, in both normal and extrinsically denervated segments of ileum. The release of this compound was prevented by tetrodotoxin and its action on the muscle was blocked when the ileum was made insensitive to the action of substance P. Experiments with transmural stimulation showed that excitatory nerve pathways involving substance P neurons extend for less than 4 cm along the intestine.

Key words

Substance P Intestine Autonomic nervous system Peptidergic nerves 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambache, N., Freeman, M. A.: Atropine-resistant longitudinal muscle spasms due to excitation of non-cholinergic neurones in Auerbach's plexus. J. Physiol. (Lond.) 199, 705–727 (1968)Google Scholar
  2. Barry, J., Dubois, M. P., Poulain, P.: LRF-producing cells of the mammalian hypothalamus. Z. Zellforsch. 146, 351–366 (1973)Google Scholar
  3. Brownlee, G., Johnson, E. S.: The site of the 5-hydroxytryptamine receptor on the intramural nervous plexus of the guinea-pig isolated ileum. Br. J. Pharmacol. 21, 306–322 (1963)Google Scholar
  4. Bury, R. W., Mashford, M. L.: A pharmacological investigation of synthetic substance P on the isolated guinea-pig ileum. Clin. Exp. Pharmacol. Physiol. 4, 453–461 (1977)Google Scholar
  5. Costa, M., Furness, J. B.: The sites of action of 5-hydroxytryptamine in nerve-muscle preparations from the guinea-pig small intestine and colon. Br. J. Pharmacol. 65, 237–248 (1979)Google Scholar
  6. Costa, M., Patel, Y., Furness, J. B., Arimura, A.: Evidence that some intrinsic neurons of the intestine contain somatostatin. Neurosci. Lett. 6, 215–222 (1977)Google Scholar
  7. Franco, R., Costa, M., Furness, J. B.: Evidence for the release of endogenous substance P from intestinal nerves. Naunyn-Schmiedeberg's Arch. Pharmacol. (in press, 1979)Google Scholar
  8. Furness, J. B.: An electrophysiological study of the innervation of the smooth muscle of the colon. J. Physiol. (Lond.) 205, 549–562 (1969)Google Scholar
  9. Furness, J. B.: Nerve-muscle preparations of large intestine. In: Methods in Pharmacology (E. E. Daniel and D. M. Paton, eds.), vol. 3, chapt. 20, pp. 385–390. New York: Plenum Press 1975Google Scholar
  10. Furness, J. B., Costa, M.: Morphology and distribution of intrinsic adrenergic neurones in the proximal colon of the guinea-pig. Z. Zellforsch. 120, 346–363 (1971)Google Scholar
  11. Furness, J. B., Costa, M.: The use of glyoxylic acid for the fluorescence histochemical demonstration of peripheral stores of noradrenaline and 5-hydroxytryptamine in whole mounts. Histochemistry 41, 335–352 (1975)Google Scholar
  12. Furness, J. B., Costa, M.: Distribution of intrinsic nerve cell bodies and axons which take up aromatic amines and their precursors in the small intestine of the guinea-pig. Cell Tiss. Res. 188, 527–543 (1978)Google Scholar
  13. Furness, J. B., Costa, M., Freeman, C. G.: Absence of tyrosine hydroxylase activity and dopamine β-hydroxylase immunoreactivity in intrinsic nerves of the guinea-pig ileum. Neuroscience 4, 305–310 (1979)Google Scholar
  14. Gabella, G.: Innervation of the intestinal muscular coat. J. Neurocytology 1, 341–362 (1972)Google Scholar
  15. Gaddum, J. H.: Tryptamine receptors. J. Physiol. (Lond.) 119, 363–368 (1953)Google Scholar
  16. Hökfelt, T., Kellerth, J., Nilsson, G., Pernow, B.: Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 100, 235–252 (1975)Google Scholar
  17. Hutchinson, M., Kosterlitz, H. W., Gilbert, J. C.: Effects of physostigmine and electrical stimulation on the acetylcholine content of the guinea-pig ileum. Eur. J. Pharmacol. 39, 221–235 (1976)Google Scholar
  18. Juorio, A. V., Gabella, G.: Noradrenaline in the guinea-pig alimentary canal: regional distribution and sensitivity to degerneration and reserpine. J. Neurochem. 22, 851–858 (1974)Google Scholar
  19. Katayama, Y., North, R. A.: Does substance P mediate slow synaptic excitation within the myenteric plexus. Nature 274, 387–388 (1978)Google Scholar
  20. Lembeck, F., Zetler, G.: Pharmacology of naturally occurring polypeptides and lipid-soluble acids. In: International encyclopaedia of pharmacology and therapeutics (J. M. Walker, ed.), sec. 72, vol. 1, pp. 29–71. Oxford: Pergamon Press 1971Google Scholar
  21. Nilsson, G., Larsson, L. I., Håkanson, R., Brodin, E., Pernow, B., Sundler, F.: Localization of substance P-like immunoreactivity in mouse gut. Histochemistry 43 97–99 (1975)Google Scholar
  22. Paton, W. D. M., Zar, A. B.: The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J. Physiol. (Lond.) 194, 13–33 (1968)Google Scholar
  23. Pearse, A. G. E., Polak, J. M.: Immunocytochemical localization of substance P in mammalian intestine. Histochemistry 41, 373–375 (1975)Google Scholar
  24. Schultzberg, M., Dreyfus, C. F., Gershon, M. D., Hökfelt, T., Elde, R. P., Nilsson, G., Said, S., Goldstein, M.: VIP-enkephalin-, substance P-, and somatostatin-like immunoreactivity in neurons intrinsic to the intestine: immunohistochemical evidence from organotypic tissue cultures. Brain Res. 155, 239–248 (1978)Google Scholar
  25. Sundler, F., Håkanson, R., Larsson, L. I., Brodin, E., Nilsson, G.: Substance P in the gut: an immunochemical and immunohis-tochemical study of its distribution and development. In: Substance P (U. S. V. Euler and B. Pernow, eds.), pp. 59–65. New York: Raven Press 1977Google Scholar
  26. Szolcsányi, J., Barthó, L.: New tyoe of nerve-mediated cholinergic contractions of the guinea-pig small intestine and its selective blockade by capsaicin. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 83–90 (1978)Google Scholar
  27. Uvnäs-Wallensten, K.: Release of substance P-like immunoreactivity into the antral lumen of cats. Acta Physiol. Scand 104, 464–468 (1978)Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • R. Franco
    • 1
  • M. Costa
    • 1
  • J. B. Furness
    • 1
  1. 1.Centre for Neuroscience and Departments of Human Physiology and MorphologyThe Flinders University of South AustraliaBedford Park

Personalised recommendations