Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 May;97(1):77–82. doi: 10.1111/j.1476-5381.1989.tb11926.x

Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin.

S D Brain 1, T J Williams 1
PMCID: PMC1854478  PMID: 2470460

Abstract

1. The mechanisms involved in tachykinin-induced oedema were investigated in rat skin and interactions between the tachykinins and calcitonin gene-related peptide (CGRP) were studied. 2. Intradermal injections of the tachykinins, substance P, neurokinin A and neurokinin B, stimulated local oedema formation which was in each case potentiated by co-injection of the vasodilator CGRP. Oedema induced by substance P, in the presence and absence of CGRP, was significantly inhibited by pretreatment of rats with a combination of the histamine H1 antagonist, mepyramine, and the 5-hydroxytryptamine antagonist, methysergide. Oedema induced by neurokinin A or B was not inhibited by this pretreatment. 3. Intradermally-injected CGRP induced a long lasting increase in local blood flow, which was measured with a laser Doppler blood flow meter. The simultaneous injection of substance P, but not of the structurally-related neurokinins, caused a loss of the prolonged vasodilator activity of CGRP. 4. These results show that oedema induced by substance P is partially dependent on mast cell amines and that only substance P causes a loss of the prolonged vasodilator activity of CGRP. 5. We suggest that the ability of substance P to prevent the persistent vasodilator activity of CGRP may be a direct consequence of substance P-induced activation of mast cells.

Full text

PDF
77

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brain S. D., Tippins J. R., Morris H. R., MacIntyre I., Williams T. J. Potent vasodilator activity of calcitonin gene-related peptide in human skin. J Invest Dermatol. 1986 Oct;87(4):533–536. doi: 10.1111/1523-1747.ep12455620. [DOI] [PubMed] [Google Scholar]
  2. Brain S. D., Williams T. J. Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased vascular permeability. Br J Pharmacol. 1985 Dec;86(4):855–860. doi: 10.1111/j.1476-5381.1985.tb11107.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brain S. D., Williams T. J. Substance P regulates the vasodilator activity of calcitonin gene-related peptide. Nature. 1988 Sep 1;335(6185):73–75. doi: 10.1038/335073a0. [DOI] [PubMed] [Google Scholar]
  4. Brain S. D., Williams T. J., Tippins J. R., Morris H. R., MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature. 1985 Jan 3;313(5997):54–56. doi: 10.1038/313054a0. [DOI] [PubMed] [Google Scholar]
  5. Caughey G. H., Leidig F., Viro N. F., Nadel J. A. Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. J Pharmacol Exp Ther. 1988 Jan;244(1):133–137. [PubMed] [Google Scholar]
  6. Chahl L. A. Interactions of substance P with putative mediators of inflammation and ATP. Eur J Pharmacol. 1977 Jul 1;44(1):45–49. doi: 10.1016/0014-2999(77)90114-5. [DOI] [PubMed] [Google Scholar]
  7. Chang M. M., Leeman S. E., Niall H. D. Amino-acid sequence of substance P. Nat New Biol. 1971 Jul 21;232(29):86–87. doi: 10.1038/newbio232086a0. [DOI] [PubMed] [Google Scholar]
  8. Devillier P., Regoli D., Asseraf A., Descours B., Marsac J., Renoux M. Histamine release and local responses of rat and human skin to substance P and other mammalian tachykinins. Pharmacology. 1986;32(6):340–347. doi: 10.1159/000138190. [DOI] [PubMed] [Google Scholar]
  9. Foreman J. C., Jordan C. C., Oehme P., Renner H. Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. J Physiol. 1983 Feb;335:449–465. doi: 10.1113/jphysiol.1983.sp014543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fuller R. W., Conradson T. B., Dixon C. M., Crossman D. C., Barnes P. J. Sensory neuropeptide effects in human skin. Br J Pharmacol. 1987 Dec;92(4):781–788. doi: 10.1111/j.1476-5381.1987.tb11381.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gamse R., Saria A. Potentiation of tachykinin-induced plasma protein extravasation by calcitonin gene-related peptide. Eur J Pharmacol. 1985 Aug 7;114(1):61–66. doi: 10.1016/0014-2999(85)90520-5. [DOI] [PubMed] [Google Scholar]
  12. Gervasoni J. E., Jr, Conrad D. H., Hugli T. E., Schwartz L. B., Ruddy S. Degradation of human anaphylatoxin C3a by rat peritoneal mast cells: a role for the secretory granule enzyme chymase and heparin proteoglycan. J Immunol. 1986 Jan;136(1):285–292. [PubMed] [Google Scholar]
  13. Gibbins I. L., Furness J. B., Costa M., MacIntyre I., Hillyard C. J., Girgis S. Co-localization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs. Neurosci Lett. 1985 Jun 12;57(2):125–130. doi: 10.1016/0304-3940(85)90050-3. [DOI] [PubMed] [Google Scholar]
  14. Gibbins I. L., Wattchow D., Coventry B. Two immunohistochemically identified populations of calcitonin gene-related peptide (CGRP)-immunoreactive axons in human skin. Brain Res. 1987 Jun 23;414(1):143–148. doi: 10.1016/0006-8993(87)91335-7. [DOI] [PubMed] [Google Scholar]
  15. Holloway G. A., Jr, Watkins D. W. Laser Doppler measurement of cutaneous blood flow. J Invest Dermatol. 1977 Sep;69(3):306–309. doi: 10.1111/1523-1747.ep12507665. [DOI] [PubMed] [Google Scholar]
  16. Hökfelt T., Kellerth J. O., Nilsson G., Pernow B. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 1975 Dec 19;100(2):235–252. doi: 10.1016/0006-8993(75)90481-3. [DOI] [PubMed] [Google Scholar]
  17. Kangawa K., Minamino N., Fukuda A., Matsuo H. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun. 1983 Jul 29;114(2):533–540. doi: 10.1016/0006-291x(83)90813-6. [DOI] [PubMed] [Google Scholar]
  18. Le Greves P., Nyberg F., Terenius L., Hökfelt T. Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. Eur J Pharmacol. 1985 Sep 24;115(2-3):309–311. doi: 10.1016/0014-2999(85)90706-x. [DOI] [PubMed] [Google Scholar]
  19. Lembeck F., Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(2):175–183. doi: 10.1007/BF00500282. [DOI] [PubMed] [Google Scholar]
  20. Minamino N., Kangawa K., Fukuda A., Matsuo H. Neuromedin L: a novel mammalian tachykinin identified in porcine spinal cord. Neuropeptides. 1984 Mar;4(2):157–166. doi: 10.1016/0143-4179(84)90126-4. [DOI] [PubMed] [Google Scholar]
  21. Piotrowski W., Foreman J. C. Some effects of calcitonin gene-related peptide in human skin and on histamine release. Br J Dermatol. 1986 Jan;114(1):37–46. doi: 10.1111/j.1365-2133.1986.tb02777.x. [DOI] [PubMed] [Google Scholar]
  22. Repke H., Piotrowski W., Bienert M., Foreman J. C. Histamine release induced by Arg-Pro-Lys-Pro(CH2)11CH3 from rat peritoneal mast cells. J Pharmacol Exp Ther. 1987 Oct;243(1):317–321. [PubMed] [Google Scholar]
  23. Williams T. J., Morley J. Prostaglandins as potentiators of increased vascular permeability in inflammation. Nature. 1973 Nov 23;246(5430):215–217. doi: 10.1038/246215a0. [DOI] [PubMed] [Google Scholar]
  24. Williams T. J., Peck M. J. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977 Dec 8;270(5637):530–532. doi: 10.1038/270530a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES