Skip to main content
Log in

Calcitonin gene-related peptide augments parasympathetic contraction of rabbit tracheal smooth musclein vitro

  • Allergy, Histamine und Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

The effect of calcitonin gene-related peptide (CGRP) on parasympathetic contraction of rabbit airway smooth muscle was studied under isometric conditionsin vitro. CGRP (10−7 M) did not contract tracheal smooth muscle, but it potentiated the contractile response to electrical field stimulation (EFS) in a dose-dependent manner, the maximal increase from the baseline response being 14.4±6.2%. In contrast, the contractile responses to exogenously administered acetylcholine were not altered by this peptide. The CGRP-induced potentiation of the contractile responses to EFS was further augmented by physostigmine (123.1%), but not influenced by phentolamine, propranolol, indomethacin, or thiorphan, an enkephalinase inhibitor. These results suggest that CGRP augments the neurally mediated contraction of rabbit airway smooth muscle probably through a prejunctional mechanism and that this effect may not be modulated by tissue enkephalinase.

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

Access this article

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. S. G. Amara, V. Jonas, M. G. Rosenfeld, E. S. Ong and R. M. Evans,Alternative RNA proceeding in calcitonine gene expression generates mRNAs encoding different polypeptide products. Nature298, 240–244 (1982).

    PubMed  Google Scholar 

  2. M. G. Rosenfeld, J.-J. Mermod, S. G. Amara, L. W. Swanson, P. E. Sawchenko, J. River, W. W. Vale and R. M. Evans,Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature304, 129–135 (1983).

    PubMed  Google Scholar 

  3. I. L. Gibbins, J. B. Furness, M. Costa, I. MacIntyre, C. J. Hillyard and S. Girgis,Co-localization of calcitonin gene-releated peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs. Neurosci. Letts.57, 125–130 (1985).

    Article  Google Scholar 

  4. J. R. Clague, C. Sternini and N. C. Brecha,Localization of calcitonin gene-related peptide-like immunoreactivity in neurons of the rat gastrointestinal tract. Neurosci. Letts.56, 63–68 (1985).

    Article  Google Scholar 

  5. G. Terenghi, J. M. Polak, J. Rodrigo, P. K. Mulderry and S. R. Bloom,Calcitonin gene-related peptide-immunoreactive nerves in the tongue, epiglottis and pharynx of the rat: occurrence, distribution and origin. Brain Res.365, 1–14 (1986).

    Article  PubMed  Google Scholar 

  6. A. Cadieux, D. R. Springall, P. K. Mulderry, J. Rodrigo, M. A. Ghatei, G. Terenghi, S. R. Bloom and J. M. Polak,Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat low respiratory tract: effect of capsaicin treatment and surgical denervations. Neurosci.19, 605–627 (1986).

    Article  Google Scholar 

  7. J. M. Lauweryns and L. V. Ranst,Calcitonin gene related peptide immunoreactivity in rat lung: light and electron microscopic study. Thorax42, 183–189 (1987).

    PubMed  Google Scholar 

  8. X.-Y. Hua,Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. Acta Physiol. Scand. Suppl.551, 1–45 (1986).

    Google Scholar 

  9. R. Uddman, A. Luts and F. Sundler,Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear Cell Tissue. Res.241, 551–555 (1985).

    Article  PubMed  Google Scholar 

  10. J. M. Lundberg, A. Franco-Cereceda, X. Hua, T. Hökfelt and J. A. Fischer,Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur. J. Pharmacol.108, 315–319 (1985).

    Article  PubMed  Google Scholar 

  11. C.-R. Martling, A. Saria, J. A. Fischer, T. Hökfelt and J. M. Lundberg,Calcitonin gene-related peptide and the lung: neuronal coexistence with substance P, release by capsaicin and vasodilatory effect. Reg. Pep.20, 125–139 (1988).

    Article  Google Scholar 

  12. S. D. Brain, T. J. Williams, J. R. Tippins, H. R. Morris and I. MacIntyre,Calcitonin gene-related peptide is a potent vasodilator. Nature313, 54–56 (1985).

    PubMed  Google Scholar 

  13. J. B. D. Palmer, F. M. C. Cuss, P. K. Mulderry, M. A. Ghatei, D. R. Springall, A. Cadieux, J. M. Polak and P. J. Barnes,Calcitonin gene-related peptide is localised to human airway nerves and potently constricts human airway smooth muscle. Br. J. Pharmacol.91, 95–101 (1987).

    PubMed  Google Scholar 

  14. D. J. Dusser, J. A. Nadel, K. Sekizawa, P. D. Graf and D. B. Borson,Neutral endopeptidase and angiotensin converting enzyme inhibitors potentiate kinin-induced contraction of ferret trachea. J. Pharmacol. Exp. Ther.224, 531–536 (1988).

    Google Scholar 

  15. J. Tamaoki, K. Kobayashi, N. Sakai, A. Chiyotani, T. Kanemura and T. Takizawa,Effect of bradykinin on airway ciliary motility and its modulation by neutral endopeptidase. Am. Rev. Repir. Dis.140, 430–435 (1989).

    Google Scholar 

  16. K. Sekizawa, J. Tamaoki, P. D. Graf, C. B. Basbaum, D. B. Borson and J. A. Nadel,Enkephalinase inhibitor potentiates mammalian tachykinin-induced contraction in ferret trachea. J. Pharmacol. Exp. Ther.243, 1211–1217 (1987).

    PubMed  Google Scholar 

  17. P. L. Greves, F. Nyberg, T. Hökfelt and L. Terenius,Calcitonin gene-related peptide is metabolized by an endopeptidase hydrolyzing substance P. Reg. Pep.25, 277–286 (1989).

    Article  Google Scholar 

  18. S. Leander, R. Håkanson, S. Rosell, K. Folkers, F. Sundler and K. Tornqvist,A specific substance P antagonist blocks smooth muscle contractions induced by non-cholinergic, non-adrenergic nerve stimulation. Nature294, 467–469 (1981).

    Article  PubMed  Google Scholar 

  19. D. T. Tanaka and M. M. Grunstein,Effect of substance P on neurally mediated contraction of rabbit airway smooth muscle. J. Appl. Physiol.60, 458–463 (1986).

    PubMed  Google Scholar 

  20. B. P. Roques, M. C. Fournié-Zaluski, E. Soroca, J. M. Lecomte, B. Malfroy, C. Llorens and J.-C. Schwartz,The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. Nature288, 286–288 (1980).

    Article  PubMed  Google Scholar 

  21. J. G. Martin and B. Collier,Acetylcholine release from canine isolated airway is not modulated by norepinephrine. J. Appl. Physiol.61, 1025–1030 (1986).

    PubMed  Google Scholar 

  22. D. Crossman, J. McEwan, J. MacDermot, I. MacIntyre and C. T. Dollery,Human calcitonin gene-related peptide activates adenylate cyclase and release prostacyclin from human umbilical vein endothelial cells. Br. J. Pharmacol.92, 695–701 (1987).

    PubMed  Google Scholar 

  23. P. J. Barnes, D. C. Crossman and R. W. Fuller,Cutaneous effects of neuropeptides are dependent upon both histamine and cyclooxygenase products. Br. J. Pharmacol.90, 100 p. (1987).

  24. H. Nakanishi, H. Yoshida, N. Nakahata and T. Suzuki,Effects of prostaglandins on excitatory transmission in isolated canine tracheal muscle. Jpn. J. Pharmacol.28, 883–889 (1978).

    PubMed  Google Scholar 

  25. J. Tamaoki, K. Sekizawa, P. D. Graf and J. A. Nadel,Cholinergic neuromodulation by prostaglandin D 2 in canine airway smooth muscle. J. Appl. Physiol.63, 1396–1400 (1987).

    PubMed  Google Scholar 

  26. J. Tamaoki, K. Sekizawa, M. L. Osborne, I. F. Ueki, P. D. Graf and J. A. Nadel,Platelet aggregation increases cholinergic neurotransmission in canine airway. J. Appl. Physiol.62, 2246–2251 (1987).

    PubMed  Google Scholar 

  27. T. Yamaguchi, B. Hitzig and R. F. Coburn,Endogenous prostaglandins and mechanical tension in canine trachealis muscle. Am. J. Physiol.230, 1737–1743 (1976).

    PubMed  Google Scholar 

  28. D. B. Borson, B. Malfroy, M. Gold, J. Ramachandran and J. A. Nadel,Tachykinins inhibit enkephalinase activity from tracheas and lungs of ferrets. Physiologist29, 174 (1986).

    Google Scholar 

  29. R. Matsas, A. J. Kenny and A. J. Turner,The metabolism of neuropeptides: The hydrolysis of peptides, including enkephalins, tachykinins and their analogues, by endopeptidase-24.11. Biochem. J.223, 433–440 (1984).

    PubMed  Google Scholar 

  30. J. T. Gafford, R. A. Skidgel, E. G. Erdös and L. B. Hersh,Human kidney “enkephalinase”, a neutral metalloendopeptidase that cleaves active peptides. Biochemistry,22, 3265–3271 (1983).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanemura, T., Tamaoki, J., Horii, S. et al. Calcitonin gene-related peptide augments parasympathetic contraction of rabbit tracheal smooth musclein vitro . Agents and Actions 31, 219–224 (1990). https://doi.org/10.1007/BF01997611

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01997611

Keywords

Navigation