Skip to main content
SpringerLink
Log in

Comparison of cardiovascular and bronchoconstrictor effects of substance P, substance K and other tachykinins

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The effects of substance P (SP), substance K (SK), physalaemin, eledoisin, kassinin, neuromedin K and bombesin on blood pressure, heart rate, respiratory insufflation pressure and plasma extravasation were studied in the guinea-pig.

  1. 2.

    All tachykinins except neuromedin K caused a fall in blood pressure with rather similar potency. The hypotensive response after physalaemin was comparatively more long-lasting.

  2. 3.

    SK and eledoisin (2.5 nmol×kg−1 i.v.) caused an initial bradycardia which then changed into tachycardia. The other tachykinins induced a slowly developing tachycardia. Neuromedin K (up to 40 nmol×kg−1) did not influence heart rate.

  3. 4.

    SK, kassinin and eledoisin were more potent than SP and physalaemin in increasing respiratory insufflation pressure. The effect of SK had a particularly long duration. Neuromedin K only induced a weak increase in insufflation pressure at a very high dose.

  4. 5.

    All tachykinins except neuromedin K induced an increase in vascular permeability to plasma proteins in many visceral organs, as indicated by Evans blue extravasation. The trachea and ureter were the most sensitive organs with regard to this effect. Physalaemin and eledoisin were generally more potent in increasing vascular permeability in various organs than SP and SK. The maximal permeability-increasing effect of SK was smaller than that of SP, although the potency was similar.

  5. 6.

    Bombesin increased insufflation pressure with no clearcut effects on vascular permeability.

  6. 7.

    It is concluded that in the same species, i.e. guinea-pig, several tachykinins have rather similar hypotensive action, while the vascular permeability increase to plasma proteins is especially pronounced after physalaemin and eledoisin. SK, kassinin and eledoisin have prominent bronchoconstrictor effects. Neuromedin K, however, displays poor activity in the present models. The existence of novel tachykinins such as SK in addition to SP in mammalian tissues suggests that effects seen upon antidromic stimulation of sensory nerves may be caused by several structurally related peptides.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Chahl LA (1979) The effect of putative peptide neurotransmitters on cutaneous vascular permeability in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 309:159–163

    Google Scholar 

  • Chahl LA, Manley S (1980) Inflammatory peptide in spinal cord: evidence that the mediator of antidromic vasodilation is not substance P. Neurosc Lett 18:99–103

    Google Scholar 

  • Erspamer GF, Erspamer V, Piccinnell D (1980) Parallel bioassay of physalaemin and kassinin, a tachykinin dodecapeptide from skin of the African frog Kassina senegalensis. Naunyn-Schmiedeberg's Arch Pharmacol 311:61–65

    Google Scholar 

  • Erspamer V (1981) The tachykinin peptide family. Trends in Neuroscience 4:267–269

    Google Scholar 

  • Fuxe K, Agnati LF, McDonald T, Locatelli V, Hökfelt T, Dahlsgaard D-J, Battistini N, Yanaihara N, Mutt V, Cuello AC (1983) Immunohistochemical indications of gastrin-releasing peptide — bombesin-like immunoreactivity in the nervous system of the rat. Co-distribution with substance P-like immunoreactive nerve terminal systems and co-existence with substance P-like immunoreactivity in dorsal root ganglion cell bodies. Neurosc Lett 37:17–22

    Google Scholar 

  • Growcott JW, Jamieson A, Tarpey AV, Topham LD (1983) Further evidence for multiple tachykinin receptors. Eur J Pharmacol 86:59–64

    Google Scholar 

  • Holmdahl G, Håkanson R, Leander S, Rosell S, Folkers K, Sundler F (1981) A substance P antagonist [D-Pro2, D-Trp7,9]SP inhibits inflammatory responses in the rabbit eye. Science 214:1029–1031

    Google Scholar 

  • Iversen LL, Hanley MR, Sandberg BEB, Lee C-M, Pinnock RD, Watson SP (1982) Substance P receptors in the nervous system and possible receptor subtypes. In: Porter R, O'Connor M (ed) Substance P in the nervous system (Ciba Foundation Symposium 91) Pitman, London, pp 186–205

    Google Scholar 

  • Jancsó N, Jancsó-Gábor A, Szolsányi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol 31:138–151

    Google Scholar 

  • Jancsó N, Jancsó-Gábor A, Szolsányi J (1968) The role of sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat. Br J Pharmacol 32:32–41

    Google Scholar 

  • Kangawa K, Minamino N, Fukuda A, Matsuo H (1983) Neuromedin K: A novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Comm 114:533–540

    Google Scholar 

  • Kimura S, Okada M, Sugita Y, Kanazawa I, Munekata E (1983) Novel neuropeptides, neurokinin α and β, isolated from porcine spinal cord. Proc Jpn Acad 59 (B):101–104

    Google Scholar 

  • Konzett H, Rössler R (1940) Versuchsanordnung zu Untersuchungen an der Bronchialmuskulatur. Arch Exp Path Pharmacol 195:71–74

    Google Scholar 

  • Lazarus LH, Di Augustine R (1980) Radioimmunoassay for the tachykinin peptide physalemin: detection of a physalemin-like substance in rabbit stomach. Anal Biochem 107:350–357

    Google Scholar 

  • Lazarus LH, Di Augustine RP, Soldato CM (1982) A substance with immunoreactivity to the peptide physalemin in mammalian respiratory tissue. Exp Lung Res 3:329–341

    Google Scholar 

  • Lembeck F, Donnerer J, Bartho I (1982) Inhibition of neurogenic vasodilation and plasma extravasation by substance P antagonists, somatostatin and (D-Met2, Pro5)-Enkepahlinamide. Eur J Pharmacol 85:171–176

    Google Scholar 

  • Lundberg JM, Saria A (1982a) Vagal substance P nerves involved in control of vascular permeability and smooth muscle tone in trachea and bronchi. Br J Pharmacol 77:441

    Google Scholar 

  • Lundberg JM, Saria A (1982b) Capsaicin-sensitive vagal neurons involved in control of vascular permeability in rat trachea. Acta Physiol Scand 115:521–523

    Google Scholar 

  • Lundberg JM, Saria A (1982c) Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive vagal sensory neurons. Acta Physiol Scand 116:473–476

    Google Scholar 

  • Lundberg JM, Saria A (1983) Capsaicin-induced desensitization of the airway mucosa to cigarette smoke, mechanical and chemical irritants. Nature 302:251–253

    Google Scholar 

  • Lundberg JM, Brodin E, Saria A (1983a) Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs. Acta Physiol Scand 119:243–252

    Google Scholar 

  • Lundberg JM, Saria A, Brodin E, Rosell S, Folkers K (1983b) A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea-pig. Proc Natl Acad Sci, USA, 80:1120–1124

    Google Scholar 

  • Lundberg JM, Hua X, Fredholm BB (1984a) 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

    Google Scholar 

  • Lundberg JM, Brodin E, Hua X, Saria A (1984b) 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

    Google Scholar 

  • Maggio JE, Sandberg BEB, Bradley CV, Iversen LL, Santikarn S, Williams BH, Hunter JC, Hanley MR (1983) Substance K: A novel tachykinin in mammalian spinal cord. In: Skrabanek P, Powell D (eds) Substance P, Boole Press, Dublin, pp 20–21

    Google Scholar 

  • Melchiorri P, Tonelli F, Negri L (1977) Comparative circulatory effects of substance P, eledoisin and physalaemin in the dog. In: von Euler US, Pernow B (eds) Substance P, pp 311–319

  • Mizrahi J, Couture R, Caranikas S, Regoli D (1982) Pharmacological effects of peptides on tracheal smooth muscle. Pharmacology 25:39–50

    Google Scholar 

  • Nawa H, Doteuchi M, Igawo K, Inouye K, Nakanishi S (1984) Substance K: A novel mammalian tachykinin that differs from substance P in its pharmacological profile. Life Science 34:1153–1160

    Google Scholar 

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

    Google Scholar 

  • Nilsson G, Dahlberg K, Brodin E, Sundler F, Strandberg K (1977) Distribution and constrictor effect of substance P in guinea-pig tracheobronchial tissue. In: von Euler US, Pernow B (eds) Substance P, pp 75–84

  • Rosell S, Björkroth U, Xu J-C, Folkers K (1983) The pharmacological profile of a substance P (SP) antagonist. Evidence for the existence of subpopulations of SP receptors. Acta Physiol Scand 117:445–449

    Google Scholar 

  • Saria A, Lundberg JM (1983) Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues. J Neurosc Methods 8:41–49

    Google Scholar 

  • Saria A, Lundberg JM, Skofitsch G, Lembeck F (1983) Vascular protein leakage in various tissues induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge: an anatomical and pharmacological study. Arch Pharmacol 324:212–218

    Google Scholar 

  • Szeli J, Molina E, Zappia L, Bertaccini G (1977) Action of some natural polypeptides on the longitudinal muscle of the guinea-pig ileum. Eur J Pharmacol 43:285–287

    Google Scholar 

  • Theodorsson-Norheim E (1983) Computer program Kruwa. Computer code MED-71T BCTIC computer code collection. Available from Biomedical Computing Technology Information Center (BCTIC), Vanderbilt Medical Center, Nashville, Tennessee 37232, USA

    Google Scholar 

  • Theodorsson-Norheim E, Brodin E, Norheim I, Rosell S (1984) Regul Pept (in press) Antisera raised against eledoisin and kassinin detect immunoreactive material in rat tissue extracts. Tissue distribution and chromatographic characterization

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institutet, Box 60400, S-104 01, Stockholm, Sweden

    Xiaoying Hua, Jan M. Lundberg & Ernst Brodin

  2. Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden

    Elvar Theodorsson-Norheim

Authors
  1. Xiaoying Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan M. Lundberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elvar Theodorsson-Norheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ernst Brodin
    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

Hua, X., Lundberg, J.M., Theodorsson-Norheim, E. et al. Comparison of cardiovascular and bronchoconstrictor effects of substance P, substance K and other tachykinins. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 196–201 (1984). https://doi.org/10.1007/BF00512072

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00512072

Key words

Search

Navigation