Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1515–1519. doi: 10.1111/j.1476-5381.1991.tb09819.x

Time-dependent synergistic interactions between the vasodilator neuropeptide, calcitonin gene-related peptide (CGRP) and mediators of inflammation.

T L Buckley 1, S D Brain 1, M Rampart 1, T J Williams 1
PMCID: PMC1908382  PMID: 1884106

Abstract

1. The action of the long lasting neuropeptide vasodilator, calcitonin gene-related peptide (CGRP), in potentiating oedema formation and neutrophil accumulation was investigated in the dorsal skin of the rabbit, in vivo. Combinations of agents under test were administered by intradermal (i.d.) injection. Oedema formation and neutrophil accumulation were then measured by quantitative radiolabel techniques. 2. CGRP (1 x 10(-11) mol per site) potentiated neutrophil accumulation induced by zymosan activated plasma, (used as a source of C5a des Arg), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). In contrast CGRP did not induce neutrophil accumulation when injected alone. 3. Oedema formation induced by a series of chemically distinct mediators of increased microvascular permeability; bradykinin, platelet activating factor (PAF), FMLP and zymosan-activated plasma; measured 0-30 min after i.d. injection was potentiated by CGRP (1 x 10(-11) mol per site). 4. Oedema formation induced by zymosan activated plasma and FMLP but not bradykinin and PAF, was also significantly potentiated by CGRP when oedema was measured 30-60 min after i.d. injection. The potentiation of oedema induced by zymosan activated plasma measured 30-60 min after i.d. injection was not observed in the presence of the shorter acting prostanoid vasodilator prostacyclin (PGI2, 3 x 10(-10) mol per site). 5. These results suggest that CGRP, as a consequence of its sustained vasodilator activity could have prolonged potentiating effects on neutrophil accumulation and oedema formation in inflammatory conditions.

Full text

PDF
1515

Selected References

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

  1. Brain S. D., MacIntyre I., Williams T. J. A second form of human calcitonin gene-related peptide which is a potent vasodilator. Eur J Pharmacol. 1986 May 27;124(3):349–352. doi: 10.1016/0014-2999(86)90238-4. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Cadieux A., Springall D. R., Mulderry P. K., Rodrigo J., Ghatei M. A., Terenghi G., Bloom S. R., Polak J. M. Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations. Neuroscience. 1986 Oct;19(2):605–627. doi: 10.1016/0306-4522(86)90285-x. [DOI] [PubMed] [Google Scholar]
  7. Forrest M. J., Jose P. J., Williams T. J. Kinetics of the generation and action of chemical mediators in zymosan-induced inflammation of the rabbit peritoneal cavity. Br J Pharmacol. 1986 Dec;89(4):719–730. doi: 10.1111/j.1476-5381.1986.tb11176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Franco-Cereceda A., Saria A., Lundberg J. M. Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain. Acta Physiol Scand. 1989 Feb;135(2):173–187. doi: 10.1111/j.1748-1716.1989.tb08565.x. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Grönblad M., Konttinen Y. T., Korkala O., Liesi P., Hukkanen M., Polak J. M. Neuropeptides in synovium of patients with rheumatoid arthritis and osteoarthritis. J Rheumatol. 1988 Dec;15(12):1807–1810. [PubMed] [Google Scholar]
  12. Henson P. M., Larsen G. L., Webster R. O., Mitchell B. C., Goins A. J., Henson J. E. Pulmonary microvascular alterations and injury induced by complement fragments: synergistic effect of complement activation, neutrophil sequestration, and prostaglandins. Ann N Y Acad Sci. 1982;384:287–300. doi: 10.1111/j.1749-6632.1982.tb21379.x. [DOI] [PubMed] [Google Scholar]
  13. Inman R. D., Chiu B., Rabinovich S., Marshall W. Neuromodulation of synovitis: capsaicin effect on severity of experimental arthritis. J Neuroimmunol. 1989 Sep;24(1-2):17–22. doi: 10.1016/0165-5728(89)90093-3. [DOI] [PubMed] [Google Scholar]
  14. Jose P. J., Forrest M. J., Williams T. J. Detection of the complement fragment C5a in inflammatory exudates from the rabbit peritoneal cavity using radioimmunoassay. J Exp Med. 1983 Dec 1;158(6):2177–2182. doi: 10.1084/jem.158.6.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jose P. J., Moss I. K., Maini R. N., Williams T. J. Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase. Ann Rheum Dis. 1990 Oct;49(10):747–752. doi: 10.1136/ard.49.10.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. José P. J., Forrest M. J., Williams T. J. Human C5a des Arg increases vascular permeability. J Immunol. 1981 Dec;127(6):2376–2380. [PubMed] [Google Scholar]
  17. Lundberg J. M., Franco-Cereceda A., Hua X., Hökfelt T., Fischer J. A. 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. 1985 Feb 5;108(3):315–319. doi: 10.1016/0014-2999(85)90456-x. [DOI] [PubMed] [Google Scholar]
  18. Martling C. R., Saria A., Fischer J. A., Hökfelt T., Lundberg J. M. Calcitonin gene-related peptide and the lung: neuronal coexistence with substance P, release by capsaicin and vasodilatory effect. Regul Pept. 1988 Feb;20(2):125–139. doi: 10.1016/0167-0115(88)90046-8. [DOI] [PubMed] [Google Scholar]
  19. Nanayama T., Kuraishi Y., Ohno H., Satoh M. Capsaicin-induced release of calcitonin gene-related peptide from dorsal horn slices is enhanced in adjuvant arthritic rats. Neurosci Res. 1989 Aug;6(6):569–572. doi: 10.1016/0168-0102(89)90045-x. [DOI] [PubMed] [Google Scholar]
  20. Rampart M., De Smet W., Fiers W., Herman A. G. Inflammatory properties of recombinant tumor necrosis factor in rabbit skin in vivo. J Exp Med. 1989 Jun 1;169(6):2227–2232. doi: 10.1084/jem.169.6.2227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rampart M., Williams T. J. Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD18 antigen expression in vivo. Br J Pharmacol. 1988 Aug;94(4):1143–1148. doi: 10.1111/j.1476-5381.1988.tb11632.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rampart M., Williams T. J. Polymorphonuclear leukocyte-dependent plasma leakage in the rabbit skin is enhanced or inhibited by prostacyclin, depending on the route of administration. Am J Pathol. 1986 Jul;124(1):66–73. [PMC free article] [PubMed] [Google Scholar]
  23. Rosenfeld M. G., Mermod J. J., Amara S. G., Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W., Evans R. M. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature. 1983 Jul 14;304(5922):129–135. doi: 10.1038/304129a0. [DOI] [PubMed] [Google Scholar]
  24. Wallengren J., Möller H., Ekman R. Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria. Arch Dermatol Res. 1987;279(8):512–515. doi: 10.1007/BF00413281. [DOI] [PubMed] [Google Scholar]
  25. Ward P. A., Zvaifler N. J. Complement-derived leukotactic factors in inflammatory synovial fluids of humans. J Clin Invest. 1971 Mar;50(3):606–616. doi: 10.1172/JCI106531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Williams T. J. Proceedings:Simultaneous measurement of local plasma exudation and blood flow changes induced by intradermal injection of vasoactive substances, using [131I]albumen and 133Xe. J Physiol. 1976 Jan;254(1):4P–5P. [PubMed] [Google Scholar]
  29. Williams T. J. Vasoactive intestinal polypeptide is more potent than prostaglandin E2 as a vasodilator and oedema potentiator in rabbit skin. Br J Pharmacol. 1982 Nov;77(3):505–509. doi: 10.1111/j.1476-5381.1982.tb09324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES