Skip to main content
SpringerLink
Log in

Nervous control of smooth muscle by transmitters, cotransmitters and modulators

  • Reviews
  • Published:
Experientia Aims and scope Submit manuscript

Conclusion

The part played by peripheral neuroeffector control mechanisms has been underestimated. These are additional to central and ganglionic control mechanisms and are much more elaborate than originally thought. While the classical view is that the autonomic nervous system consists largely of antagonistic cholinergic and adrenergic nerves, about sixteen putative neurotransmitters have been proposed in autonomic nerves in the past few years, including various monoamines, polypeptides, purines and amino acids. Modulatory transmitter mechanisms have also been recognized, including prejunctional inhibition or enhancement of transmitter release, postjunctional modulation of transmitter action, and the secondary involvement of locally synthesized hormones and prostaglandins. The existence of more than one transmitter substance in some nerves is now widely recognized, and suggestions have been made about the ways that this can lead to differential peripheral control mechanisms at nerve terminals themselves. The cotransmitters always have synergistic actions on postjunctional effector cells, but two different operating mechanisms are postulated. 1) If both substances are stored in the same vesicles (for example, ACh or NA with ATP), release is closely parallel at all impulse frequencies. Upon release, the cotransmitter, in addition to having a direct action on postjunctional cells, may facilitate the action of the other transmitter and/or act as an inhibitor of its release. Differential actions at different impulse frequencies are achieved post-junctionally by ATP and NA acting via EJP-spike and spike-independent mechanisms, respectively. 2) If the two substances are stored in separate vesicle types (for example ACh or NA with some peptides), then differential release is possible at different impulse frequencies; the peptides released at higher frequencies modulate the role of the classical transmitter, by both prejunctional enhancement of its release and post-junctional facilitation of its action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Akasu, T., Hirai, K., and Koketsu, K., Increase of acetylcholine receptor sensitivity by adenosine triphosphate: a novel action of ATP on ACh-sensitivity. Br. J. Pharmac.74 (1981) 505–507.

    Article  CAS  Google Scholar 

  2. Brownstein, M. J., Saavedra, J. M., Axelrod, J., Zeman, G. H., and Carpenter, D. O., Co-existence of several putative neurotransmitters in single identified neurons ofAplysia. Proc. natn. Acad. Sci. USA71 (1974) 4662–4665.

    Article  CAS  Google Scholar 

  3. Bunge, R., Johnson, M., and Ross, C. D., Nature and nurtune in development of the autonomic neurone. Science199 (1978) 1409–1416.

    Article  CAS  PubMed  Google Scholar 

  4. Burnstock, G., Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmac. Rev.21 (1969) 247–324.

    CAS  Google Scholar 

  5. Burnstock, G., Structure of smooth muscle and its innervation, in: Smooth Muscle, pp. 1–69. Eds E. Bülbring, A. Brading, A. Jones and T. Tomita. Edward Arnold, London 1970.

    Google Scholar 

  6. Burnstock, G., Purinergic nerves. Pharmac. Rev.24 (1972) 509–581.

    CAS  Google Scholar 

  7. Burnstock, G., Do some nerve cells release more than one transmitter? Neuroscience1 (1976) 239–248.

    Article  CAS  PubMed  Google Scholar 

  8. Burnstock, G., Autonomic neuroeffector junctions—reflex vasodilatation of the skin. J. invest. Derm.69 (1977) 47–57.

    Article  CAS  PubMed  Google Scholar 

  9. Burnstock, G., Do some sympathetic neurones release both noradrenaline and acetylcholine? Prog. Neurobiol.11 (1978) 205–222.

    Article  CAS  PubMed  Google Scholar 

  10. Burnstock, G., Past and current evidence for the purinergic nerve hypothesis, in: Physiological and Regulatory Functions of Adenosine and Adenine Nucleotides, pp. 3–32. Eds H. P. Baer and G. I. Drummond. Raven Press, New York 1979.

    Google Scholar 

  11. Burnstock, G., Neurotransmitters and trophic factors in the autonomic nervous system. J. Physiol., Lond.313 (1981) 1–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Burnstock, G., (ed.), Purinergic Receptors, Receptors and Recognition, series B, vol. 12. Chapman & Hall, London 1981.

    Google Scholar 

  13. Burnstock, G., Cytochemical studies in the enteric nervous system, in: Cytochemical Methods in Neuroanatomy, pp. 129–149. Eds V. Chan-Palay and S. L. Palay. Alan R. Liss, New York 1982.

    Google Scholar 

  14. Burnstock, G., Neuromuscular transmitters and trophic factors, in: Advanced Medicine, vol. 18, pp. 143–148. Ed. M. Sarner. Pitman Medical, London 1982.

    Google Scholar 

  15. Burnstock, G., the cotransmitter hypothesis, with special reference to the storage and release of ATP with noradrenaline and acetylcholine, in Co-transmission, pp. 151–163. Ed. A. C. Cuello. Macmillan, London 1982.

    Google Scholar 

  16. Burnstock, G., Recent concepts of chemical communication between excitable cells, in: Dale's Principle and Communication Between Neurones, pp. 7–35. Ed. N. N. Osborne. Pergamon Press, Oxford 1983.

    Chapter  Google Scholar 

  17. Burnstock, G., Hökfelt, T., Gershon, M. D., Iversen, L. L., Kosterlitz, H. W., and Szurszewski, J. H., Non-adrenergic, non-cholinergic autonomic neurotransmission mechanisms. Neurosci. Res. Prog. Bull.17 (1979) 379–519.

    Google Scholar 

  18. Burnstock, G., Crowe, R., Kennedy, C., and Török, J., Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process. Br. J. Pharmac.82 (1984) 359–368.

    Article  CAS  Google Scholar 

  19. Burnstock, G., Griffith, S. G., and Sneddon, P., Autonomic nerves in the precapillary vessel wall. J. Cardiovasc. Pharmac.6 (1984) S344–S353.

    Article  Google Scholar 

  20. Cook, R. D., and Burnstock, G., The ultrastructure of Auerbach's plexus in the guinea-pig. I. Neuronal elements. J. Neurocytol.5 (1976) 171–194.

    Article  CAS  PubMed  Google Scholar 

  21. Cuello, A. C. (ed.), Co-transmission. Macmillan Press, London 1982.

    Google Scholar 

  22. Delbro, D., Fändriks, L., Lisander, B., and Andersson, B. A., Gastric atropine-sensitive excitation by peripheral vagal stimulation after hexamethonium. Antidromic activation of afferents. Acta physiol. scand.114 (1982) 433–440.

    Article  CAS  PubMed  Google Scholar 

  23. Docherty, J. R., and McGrath, J. C., An examination of factors influencing adrenergic transmission in the pithed rat, with special reference to noradrenaline uptake mechanisms and post-junctional alpha-adrenoceptors. Naunyn-Schmiedebergs Arch. Pharmac.313 (1980) 101–111.

    Article  CAS  Google Scholar 

  24. Edwards, A. V., and Bloom, S. R., Recent physiological studies of the alimentary autonomic innervation. Scand. J. Gastroenterol.17, Suppl. 71 (1982) 77–89.

    Google Scholar 

  25. Fedan, J. S., Hogaboom, G. K., O'Donnell, J. P., Colby, J., and Westfall, D. P., Contribution by purines to the neurogenic response of the vas deferens of the guinea-pig. Eur. J. Pharmac.69 (1981) 41–53.

    Article  CAS  Google Scholar 

  26. Furness, J. B., and Costa, M., Types of nerves in the enteric nervous system. Neuroscience5 (1980) 1–20.

    Article  CAS  PubMed  Google Scholar 

  27. Furshpan, E. J., MacLeish, P. R., O'Lague, P. H., and Potter, D. D., Chemical transmission between rat sympathetic neurones and cardiac myocytes development in microcultures—evidence for cholinergic, adrenergic and dual function neurones. Proc. natn. Acad. Sci. USA73 (1976) 4225–4229.

    Article  CAS  Google Scholar 

  28. Gabella, G., Structure of smooth muscles, in Smooth Muscle: An Assessment of Current Knowledge, pp. 1–46. Eds. E. Bülbring, A. F. Brading, A. W. Jones and T. Tomita. Edward Arnold, London 1981.

    Google Scholar 

  29. Gershon, M. D., The enteric nervous system. A. Rev. Neurosci.5 (1981) 1–20.

    Google Scholar 

  30. Gillespie, J. S., Review: Non-adrenergic, non-cholinergic inhibitory control of gastrointestinal motility, in: Motility of the Digestive Tract, pp. 51–56. Ed. M. Wienbeck. Raven Press, New York 1982.

    Google Scholar 

  31. Gustafsson, L. E., Adenosine elicits prejunctional inhibition and postjunctional enhancement in rabbit iris sphincter. Acta physiol. scand.114 (1982) 38A.

    Google Scholar 

  32. Hökfelt, T., Johansson, O., Lungdahl, A., Lundberg, J. M., and Schultzberg, M., Peptidergic neurones. Nature, Lond.284 (1980) 515–521.

    Article  PubMed  Google Scholar 

  33. Holck, M. I., and Marks, B. H., Purine nucleoside and nucleotide interactions on normal and subsensitive α-adrenoreceptor responsiveness in guinea-pig vas deferens. J. Pharmac. exp. Ther.205 (1978) 104–117.

    CAS  Google Scholar 

  34. Jahr, C. E., and Jessel, T. M., ATP excites a subpopulation of rat dorsal horn neurones. Nature, Lond.304 (1983) 730–733

    Article  CAS  PubMed  Google Scholar 

  35. Jessen, K. R., Mirsky, R., Dennison, M., and Burnstock, G., GABA may be a neurotransmitter in the vertebrate nervous system. Nature, Lond.281 (1979) 71–74.

    Article  CAS  PubMed  Google Scholar 

  36. Katsuragi, T., and Su, C., Augmentation by theophylline of [3H] purine release from vascular adrenergic nerves: evidence for presynaptic autoinhibition. J. Pharmac. exp. Ther.220 (1982) 152–156.

    CAS  Google Scholar 

  37. Kolb, H.-A., and Wakelam, M. J. O., Transmitter-like action of ATP on patched membranes of cultured myoblasts and myotubules. Nature, Lond.303 (1983) 621–623.

    Article  CAS  PubMed  Google Scholar 

  38. Langer, S. Z., and Pinto, J. E. B., Possible involvement of a transmitter different from norepinephrine in residual responses to nerve stimulation of cat nictitating membrane after pretreatment with reserpine. J. Pharmac. exp. Ther.196 (1976) 697–713.

    CAS  Google Scholar 

  39. Lundberg, J. M., Evidence for co-existence of vasoactive intestinal polypeptide (VIP) and acetylcholine in neurones of cat exocrine glands. Morphological, biochemical and functional studies. Acta physiol. scand., suppl. 496 (1981) 1–57.

    Google Scholar 

  40. Lundberg, J. M., and Saria, A., Vagal substance P nerves involved in control of vascular permeability and smooth muscle tone in trachea and bronchi. Br. J. Pharmac.77 (1982) 441P.

    Google Scholar 

  41. McDonald, D. M., and Mitchell, R. A., The neural pathway involved in ‘efferent inhibition’ of chemoreceptors in the cat carotid body. J. comp. Neurol.201 (1981) 457–476.

    Article  CAS  PubMed  Google Scholar 

  42. Meldrum, L. A., and Burnstock, G., Evidence that ATP acts as a cotransmitter with noradrenaline in sympathetic nerves supplying the guinea-pig vas deferens. Eur. J. Pharmac.92 (1983) 161–163.

    Article  CAS  Google Scholar 

  43. Moody, C., and Burnstock, G., Evidence for the presence of P1-purinoceptors on cholinergic nerve terminals in the guinea-pig ileum. Eur. J. Pharmac.77 (1982) 1–9.

    Article  CAS  Google Scholar 

  44. Morel, N., and Meunier, F.-M., Simultaneous release of acetylcholine and ATP from stimulated cholinergic synaptosomes. J. Neurochem.36 (1981) 1766–1773.

    Article  CAS  PubMed  Google Scholar 

  45. Osborne, N. N. (ed.), Dale's Principle and Communication Between Neurones. Pergamon Press, Oxford and New York 1983.

    Google Scholar 

  46. Paton, D. M., Presynaptic neuromodulation mediated by purinergic receptors, in: Purinergic Receptors, Receptors and Recognition, Series B, pp. 199–219. Ed. G. Burnstock. Chapman & Hall, London 1981.

    Google Scholar 

  47. Pearse, A. G., The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem.17 (1969) 303–313.

    Article  CAS  PubMed  Google Scholar 

  48. Potter, D. D., Furshpan, E. J., and Landis, S. C., Transmitter status in cultured rat sympathetic neurons: plasticity and multiple function. Fed. Proc.42 (1983) 1626–1632.

    CAS  PubMed  Google Scholar 

  49. Ribeiro, J. A., Purinergic modulation of transmitter release. J. theor. Biol.80 (1979) 259–270.

    Article  CAS  PubMed  Google Scholar 

  50. Rodrigo, J., Polak, J. M., Fernandez, L., Ghatei, M. A., Mulderry, P., and Bloom, S. R., CGRP-immunoreactive sensory and motor nerves in the oesophagus of rat, cat and monkey. Dig. Dis. Sci.29 (1984) 705.

    Google Scholar 

  51. Rosenfeld, M. G., Mermod, J. J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W. W., and Evans, R. M., Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature, Lond.304 (1983) 129–135.

    Article  CAS  PubMed  Google Scholar 

  52. Silinsky, E. M., On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J. Physiol., Lond.247 (1975) 145–162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sneddon, P., and Burnstock, G., Inhibition of excitatory junction potential in guinea-pig vas deferens by α,β-methylene ATP: further evidence for ATP and noradrenaline as cotransmitter. Eur. J. Pharmac.100 (1984) 85–90.

    Article  CAS  Google Scholar 

  54. Sneddon, P., Meldrum, L. A., and Burnstock, G., Control of transmitter release in guinea-pig vas deferens by prejunctional P1-purinoceptors. Eur. J. Pharmac.105 (1984) 293–299.

    Article  CAS  Google Scholar 

  55. Sneddon, P., and Westfall, D. D., Pharmacological evidence that adenosine triphosphate and noradrenaline are cotransmitters in the guinea-pig vas deferens. J. Physiol., Lond.347 (1984) 561–580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Su, C., Modes of vasoconstrictor and vasodilator neurotransmission. Blood Vessels15 (1978) 183–189.

    CAS  PubMed  Google Scholar 

  57. Su, C., Bevan, J. A., and Burnstock, G., [3H]-Adenosine triphosphate: release during stimulation of enteric nerves. Science173 (1971) 337–339.

    Article  Google Scholar 

  58. Sundler, F., Håkanson, R., Leander, S., and Uddman, R., Neuropeptides in the gut wall: cellular and subcellular localization, topographic distribution and possible physiological significance, in: Cytochemical Methods in Neuroanatomy, pp. 341–356. Eds V. Chan-Palay and S. L. Palay. Alan R. Liss, New York 1982.

    Google Scholar 

  59. Vizi, E. S., Presynaptic modulation of neurochemical transmission. Prog. Neurobiol.12 (1979) 181–290.

    Article  CAS  PubMed  Google Scholar 

  60. White, T. D., Potter, P., and Wonnacott, S., Depolarization induced release of ATP from cortical synaptosomes is not associated with acetylcholine release. J. Neurochem.34 (1980) 1109–1112.

    Article  CAS  PubMed  Google Scholar 

  61. Zimmerman, H., Dowdall, M. J., and Lane, D. A., Purine salvage at the cholinergic nerve endings of theTorpedo electric organ—central role of adenosine. Neuroscience4 (1979) 979–993.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Embryology and Centre for Neuroscience, University College London, Gower Street, WC1E 6BT, London, England

    G. Burnstock

Authors
  1. G. Burnstock
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burnstock, G. Nervous control of smooth muscle by transmitters, cotransmitters and modulators. Experientia 41, 869–874 (1985). https://doi.org/10.1007/BF01970003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01970003

Key words

Search

Navigation