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. 1993 Mar;108(3):705–710. doi: 10.1111/j.1476-5381.1993.tb12865.x

The modulation of inflammatory oedema by calcitonin gene-related peptide.

P Newbold 1, S D Brain 1
PMCID: PMC1908016  PMID: 7682134

Abstract

1. The effect of calcitonin gene-related peptide (CGRP) when given with or as a pretreatment to oedema inducing agents was investigated in the skin and paws of male Wistar and Sprague Dawley rats. 2. Oedema formation at intradermally-injected sites in the skin was measured by a 125I-labelled human serum albumin accumulation technique and paw oedema was measured by a weight displacement technique. 3. CGRP (30 pmol) when given with, or as a 20 min pretreatment, markedly potentiated oedema formation induced by substance P (100 pmol) in rat skin. In comparison, CGRP had little effect on 5-hydroxytryptamine (5-HT, 0.1-3 nmol)-induced oedema when given as a co-injection but significantly potentiated 5-HT-induced oedema when given as a 20 min pretreatment in the skin. Similar results were obtained in both Wistar and Sprague Dawley rats. 4. Pretreatment with CGRP (30 pmol) had little modulatory effect on oedema induced by substance P (100 pmol) in the presence of the vasodilator prostanoid, prostaglandin E1 (PGE1, 850 pmol) in the skin of Wistar rats. 5. Pretreatment with CGRP (30 pmol) caused a non-significant increase in carrageenin (300 micrograms)-induced oedema in the hind paw of Wistar rats. Capsaicin (100 nmol) given as a pretreatment had little effect on carrageenin-induced oedema. 6. CGRP (30 pmol), given as a pretreatment, had little modulatory effect on 5-HT (3 nmol)-induced oedema in the paw of Wistar rats but a non-significant decrease in paw oedema was observed in Sprague Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Andrews P. V., Helme R. D., Thomas K. L. NK-1 receptor mediation of neurogenic plasma extravasation in rat skin. Br J Pharmacol. 1989 Aug;97(4):1232–1238. doi: 10.1111/j.1476-5381.1989.tb12583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brain S. D., Cambridge H., Hughes S. R., Wilsoncroft P. Evidence that calcitonin gene-related peptide contributes to inflammation in the skin and joint. Ann N Y Acad Sci. 1992 Jun 30;657:412–419. doi: 10.1111/j.1749-6632.1992.tb22787.x. [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. Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin. Br J Pharmacol. 1989 May;97(1):77–82. doi: 10.1111/j.1476-5381.1989.tb11926.x. [DOI] [PMC free article] [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. Buckley T. L., Brain S. D., Collins P. D., Williams T. J. Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide. J Immunol. 1991 May 15;146(10):3424–3430. [PubMed] [Google Scholar]
  7. Buckley T. L., Brain S. D., Rampart M., Williams T. J. Time-dependent synergistic interactions between the vasodilator neuropeptide, calcitonin gene-related peptide (CGRP) and mediators of inflammation. Br J Pharmacol. 1991 Jun;103(2):1515–1519. doi: 10.1111/j.1476-5381.1991.tb09819.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cambridge H., Brain S. D. Calcitonin gene-related peptide increases blood flow and potentiates plasma protein extravasation in the rat knee joint. Br J Pharmacol. 1992 Jul;106(3):746–750. doi: 10.1111/j.1476-5381.1992.tb14404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Colpaert F. C., Donnerer J., Lembeck F. Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis. Life Sci. 1983 Apr 18;32(16):1827–1834. doi: 10.1016/0024-3205(83)90060-7. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Han S. P., Naes L., Westfall T. C. Inhibition of periarterial nerve stimulation-induced vasodilation of the mesenteric arterial bed by CGRP (8-37) and CGRP receptor desensitization. Biochem Biophys Res Commun. 1990 Apr 30;168(2):786–791. doi: 10.1016/0006-291x(90)92390-l. [DOI] [PubMed] [Google Scholar]
  14. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991 Jun;43(2):143–201. [PubMed] [Google Scholar]
  15. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience. 1988 Mar;24(3):739–768. doi: 10.1016/0306-4522(88)90064-4. [DOI] [PubMed] [Google Scholar]
  16. Hughes S. R., Brain S. D. A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin. Br J Pharmacol. 1991 Nov;104(3):738–742. doi: 10.1111/j.1476-5381.1991.tb12497.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hägermark O., Hökfelt T., Pernow B. Flare and itch induced by substance P in human skin. J Invest Dermatol. 1978 Oct;71(4):233–235. doi: 10.1111/1523-1747.ep12515092. [DOI] [PubMed] [Google Scholar]
  18. Jancsó N., Jancsó-Gábor A., Szolcsányi J. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother. 1967 Sep;31(1):138–151. doi: 10.1111/j.1476-5381.1967.tb01984.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lundblad L., Lundberg J. M., Anggård A., Zetterström O. Capsaicin pretreatment inhibits the flare component of the cutaneous allergic reaction in man. Eur J Pharmacol. 1985 Jul 31;113(3):461–462. doi: 10.1016/0014-2999(85)90098-6. [DOI] [PubMed] [Google Scholar]
  20. Maggi C. A., Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol. 1988;19(1):1–43. doi: 10.1016/0306-3623(88)90002-x. [DOI] [PubMed] [Google Scholar]
  21. Matsuse T., Thomson R. J., Chen X. R., Salari H., Schellenberg R. R. Capsaicin inhibits airway hyperresponsiveness but not lipoxygenase activity or eosinophilia after repeated aerosolized antigen in guinea pigs. Am Rev Respir Dis. 1991 Aug;144(2):368–372. doi: 10.1164/ajrccm/144.2.368. [DOI] [PubMed] [Google Scholar]
  22. McCusker M. T., Chung K. F., Roberts N. M., Barnes P. J. Effect of topical capsaicin on the cutaneous responses to inflammatory mediators and to antigen in man. J Allergy Clin Immunol. 1989 Jun;83(6):1118–1124. doi: 10.1016/0091-6749(89)90455-7. [DOI] [PubMed] [Google Scholar]
  23. Raud J., Dahlén S. E., Sydbom A., Lindbom L., Hedqvist P. Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2315–2319. doi: 10.1073/pnas.85.7.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raud J., Lundeberg T., Brodda-Jansen G., Theodorsson E., Hedqvist P. Potent anti-inflammatory action of calcitonin gene-related peptide. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1429–1435. doi: 10.1016/s0006-291x(05)81356-7. [DOI] [PubMed] [Google Scholar]
  25. Raud J., Sydbom A., Dahlén S. E., Hedqvist P. Prostaglandin E2 prevents diclofenac-induced enhancement of histamine release and inflammation evoked by in vivo challenge with compound 48/80 in the hamster cheek pouch. Agents Actions. 1989 Aug;28(1-2):108–114. doi: 10.1007/BF02022990. [DOI] [PubMed] [Google Scholar]
  26. Raychaudhuri A., Colombo C., Pastor G., Wong M., Jeng A. Y. Effect of capsaicin on carrageenan-induced inflammation in rat pleurisy and exudate substance P level. Agents Actions. 1991 Sep;34(1-2):251–253. doi: 10.1007/BF01993295. [DOI] [PubMed] [Google Scholar]
  27. Spina D., McKenniff M. G., Coyle A. J., Seeds E. A., Tramontana M., Perretti F., Manzini S., Page C. P. Effect of capsaicin on PAF-induced bronchial hyperresponsiveness and pulmonary cell accumulation in the rabbit. Br J Pharmacol. 1991 May;103(1):1268–1274. doi: 10.1111/j.1476-5381.1991.tb12335.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. WINTER C. A., RISLEY E. A., NUSS G. W. ANTI-INFLAMMATORY AND ANTIPYRETIC ACTIVITIES OF INDOMETHACIN, 1-(P-CHLOROBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID. J Pharmacol Exp Ther. 1963 Sep;141:369–376. [PubMed] [Google Scholar]
  29. 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]

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