Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Calcitonin gene-related peptide (CGRP) and capsaicin-induced stimulation of heart contractile rate and force

  • 120 Accesses

  • 158 Citations


  1. 1.

    The effects of calcitonin gene-related peptide (CGRP) on guinea-pig heart contractility were investigated in vitro in relation to the responce of capsaicin and noradrenaline (NA).

  2. 2.

    Synthetic rat CGRP (>10−8 M) caused a long-lasting, positive inotropic and chronotropic effect on the spontaneously beating right atrium. The response to CGRP mimicked the effects of capsaicin and was resistant to betaadrenoceptor blockade using metoprolol. Furthermore, CGRP did not change basal efflux or the release of3H-NA induced by transmural nerve stimulation, suggesting an action independent of sympathetic mechanisms. Mepyramine and cimetidine did not reduce the response to CGRP.

  3. 3.

    After tachyphylaxis to the effects of CGRP (5×10−7M) which developed within 15–20 min, the positive inotropic and chronotropic atrial response to capsaicin was abolished. The effects of NA, however, were not influenced by CGRP tachyphylaxis.

  4. 4.

    In the isolated perfused whole heart, CGRP had more pronounced stimulatory effects on ventricular contractile rate than on force compared to NA. The CGRP response was resistant to metoprolol and still present in capsaicin-pretreated animals. Capsaicin caused a slight initial inhibition of ventricular contractility, which was followed by a marked stimulatory action. As for CGRP, the cardio-excitatory response to capsaicin was more pronounced on rate than on force. The stimulatory reponses to capsaicin were absent 2 weeks after systemic capsaicin pretreatment.

In conclusion, CGRP mimics the non-adrenergic, cardioexcitatory effects of capsaicin, and the capsaicin response is absent after CGRP tachyphylaxis. Therefore, it is suggested that release of CGRP from local sensory nerves within the heart underlies the cardiostimulatory response to capsaicin.

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


  1. Broadley KJ (1978) The Langendorff heart preparation — Reappraisal of its role as research and teaching model for coronary vasoactive drugs. J Pharmacol Methods 190:431–450

  2. Dahlöf C, Ljung B, Åblad B (1980) Pre- and postjunctional beta-adrenoceptor-mediated effector response in the isolated rat portal vein. Acta Physiol Scand 108:39–47

  3. Franco-Cereceda A, Lundberg JM, Henke H, Petermann JB, Hökfelt T, Fischer JA (1985) Calcitonin gene-related peptide CGRP in capsaicin-sensitive sensory neurons: Distribution and release by capsaicin. Cell Tissue Res (in press)

  4. Fukuda N, Fujiwara M (1969) Effect of capsaicin on the guinea-pig isolated atrium. J Pharm Pharmacol 21:622–624

  5. Gamse R, Molnar A, Lembeck F (1979) Substance P release from spinal cord slices by capsaicin. Life Sci 25:629–636

  6. Gamse R, Wax A, Zigmond RE, Leeman S (1981) Immunoreactive substance P in sympathetic ganglia: Distribution and sensitivity towards capsaicin. Neuroscience 6:437–441

  7. Häggendahl J, Johansson B, Jonanson J, Ljung B (1970) Correlation between noradrenaline release and effector response to nerve stimulation in the rat portal vein in vitro. Acta Physiol Scand [Suppl] 349:17–32

  8. Lembeck F, Donnerer J (1981) Postocclusive cutaneous vasodilation mediated by substance P. Naunyn-Schmiedeberg's Arch Pharmacol 316:165–171

  9. Lundberg JM, Brodin E, Hua X, Saria A (184a) Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig. Acta Physiol Scand 120:217–227

  10. Lundberg JM; Hua X, Fredholm B (1984b) Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes? Naunyn-Schmiedeberg's Arch Pharmacol 325:176–182

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

  12. Molnar J, György L Unyi G, Kenyeres J (1969) The effect of capsaicin on the isolated guinea-pig ileum and auricle. Acta Physiol Acad Sci Hung 35:369–374

  13. Moyland R, Westfall TC (1977) Adenosine effects on the field-stimulation induced release of3H-norepinephrine from the rat portal vein. The Pharmacologist 19:240

  14. Nawa H, Hirose T, Takashima H, Ianyama S, Nakanishi S (1983) Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature 306:32–36

  15. Papka RE, Furness JB, Della NG, Costa M (1981) Depletion by capsaicin of substance P immunoreactivity from nerve fibres in the guinea-pig heart. Neurosci Lett 27:47–53

  16. Papka RE, Furness JB, Della NG, Murphy R, Costa M (1984) Time course effect of capsaicin on ultrastructure and histochemistry of substance P-immunoreactive nerves associated with the cardiovascular system of the guinea-pig. Neuroscience 12:1277–1292

  17. Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko P, Rivier J, Vale W, Evans R (1983) Production of a novel neuropeptide by the calcitonin gene via tissue specific RNA processing. Nature 304:129–132

  18. Saria A, Lundberg JM, Hua X, Lembeck F (1984) Sensory control of vascular permeability and capsaicin-induced substance P release from the guinea-pig ureter. Neursci Lett 41:167–172

  19. Saria A, Theodorsson-Norheim E, Gamse R, Lundberg JM (1984) Release of substance P- and sbstance K-like immunoreactivities from isolated perfused guinea-pig lung. Eur J Pharmacol 106:207–208

  20. Tippins JR, Morris HR, Panico M, Bevis P, Girgis B, Mac Intyre I, Azvia M, Attinger M (1984) The myotropic and plasma calcium modulating effects of calcitonin gene related peptide (CGRP). Neuropeptides 4:425–434

  21. Virus RM, Gebhart G-F (1979) Pharmacological actions of capsaicin: Apparent involvement of substance P and serotonin. Life Sci 25:1273–1284

  22. Wiesenfeld-Hallin Z, Hökfelt T, Lundberg JM, Forssman WG, Reinecke M, Tschopp F, Fischer JA (1984) Immunoreactive calcitonin-gene related peptide and substance P co-exist in sensory neurons to the spinal cord and interact in spinal behavioural responses of the rat. Neurosci Lett 52:199–204

  23. Zernig G, Holzer P, Lembeck F (1984) A study of the mode and site of action of capsaicin in guinea-pig heart and rat uterus. Naunyn-Schmiedeberg's Arch Pharmacol 326:58–63

Download references

Author information

Correspondence to Jan M. Lundberg.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Franco-Cereceda, A., Lundberg, J.M. Calcitonin gene-related peptide (CGRP) and capsaicin-induced stimulation of heart contractile rate and force. Naunyn-Schmiedeberg's Arch. Pharmacol. 331, 146–151 (1985). https://doi.org/10.1007/BF00634231

Download citation

Key words

  • Calcitonin-gene related peptide (CGRP)
  • Capsaicin
  • Sensory nerves
  • Heart