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.
Similar content being viewed by others
References
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).
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).
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).
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).
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).
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).
J. M. Lauweryns and L. V. Ranst,Calcitonin gene related peptide immunoreactivity in rat lung: light and electron microscopic study. Thorax42, 183–189 (1987).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
J. G. Martin and B. Collier,Acetylcholine release from canine isolated airway is not modulated by norepinephrine. J. Appl. Physiol.61, 1025–1030 (1986).
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).
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).
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).
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).
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).
T. Yamaguchi, B. Hitzig and R. F. Coburn,Endogenous prostaglandins and mechanical tension in canine trachealis muscle. Am. J. Physiol.230, 1737–1743 (1976).
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).
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).
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).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01997611