Skip to main content
Log in

A bradykinin antagonist inhibits carrageenan edema in rats

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

Summary

Bradykinin has been implicated in acute inflammatory reactions. Intradermal injection elicits increased vascular permeability and hyperalgesia, and bioassays have suggested increased bradykinin concentration in inflammatory exudates. Poorly specific inhibitors of kallikrein, the enzyme catalyzing formation of bradykinin, inhibit certain acute inflammatory reactions. However, the lack of a specific bradykinin receptor antagonist has made proof of the hypothesis difficult. In this study, we have used the potent, specific bradykinin antagonist DArg[Hyp3DPhe7] bradykinin (NPC 567) as a probe to examine the role of bradykinin in carrageenan-induced edema in the paws of rats. Subplantar injection of carrageenan led to an increase in immunoreactive bradykinin and metabolic product, desArg9bradykinin. NPC 567 inhibited the development of edema in response to carrageenan, to a maximum 65%. Thus, bradykinin appears to be a major mediator of increased vascular permeability in response to carrageenan.

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

Access this article

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

  • Abraham WM (1989) Role of bradykinin in a sheep model of allergic asthma. In: Burch RM (ed) Bradykinin Antagonists: Basic and Clinical Research. Dekker, New York (in press)

    Google Scholar 

  • Capasso F, Balestrieri B, diRosa M, Persico P, Sorrentino L (1975) Enhancement of carrageenan foot oedema by 1,10-phenanthroline and evidence for the bradykinin as endogenous mediator. Agents Actions 5:359–363

    Google Scholar 

  • Eizirik DL, DeLucio MA, Boschero AC, Hoffmann ME (1987) 1,10-Phenanthroline, a metal chelator, protects against alloxanbut not streptozotocin-induced diabetes. J Free Rad Biol Med 2:189–192

    Google Scholar 

  • Farmer SG, Burch RM (1990) Pharmacology of bradykinin antagonists. In: Burch RM (ed) Bradykinin antagonists: basic and clinical research, Dekker, New York (in press)

    Google Scholar 

  • Farmer SG, Burch RM, Meeker SA, Wilkins DE (1989) Evidence for a pulmonary B3 bradykinin receptor. Mol Pharmacol 36:1–8

    Google Scholar 

  • Griesbacher T, Lembeck F (1987) Effect of bradykinin antagonists on bradykinin-induced plasma extravasation, venoconstriction, prostaglandin Ez release, nociceptor stimulation and contractraction of the iris sphincter muscle in the rabbit. Br J Pharmacol 92:333–340

    Google Scholar 

  • Hargreaves KM, Troullos ES, Dionne RA, Schmidt EA, Schafer SC, Joris JL (1988) Bradykinin is increased during acute and chronic inflammation: therapeutic implications. Clin Pharmacol Ther 44:613–621

    Google Scholar 

  • Marceau F, Lussier A, Regoli D, Giroud JP (1983) Pharmacology of the kinins: Their relevance to tissue injury and inflammation. Gen Pharmacol 14:209–229

    Google Scholar 

  • Regoli D, Barabe (1980) Pharmacology of bradykinin and related kinins. Pharmacol Rev 32:1–46

    Google Scholar 

  • Spragg J, Vavrek RJ, Stewart JM (1988) The inhibition of glandular kallikrein by peptide analog antagonists of bradykinin. Peptides 9:203–206

    Google Scholar 

  • Steranka LR, Rodriguez R, DeHaas CJ (1988) Effects of bradykinin antagonists on vascular permeability in rat skin. Pharmacologist 30:A30

    Google Scholar 

  • Stewart JM, Vavrek RJ (1990) Chemistry of peptide B2 bradykinin antagonists. In: Burch RM (ed) Bradykinin antagonists: basic and clinical research, New York, Dekker (in press)

    Google Scholar 

  • Tiffany CW, Burch RM (1989) Bradykinin stimulates tumor necrosis factor and interleukin 1 release from macrophages. FEBS Lett 247:189–192

    Google Scholar 

  • Togo J, Burch RM, DeHaas CJ, Connor JR, Steranka LR (1989). D-Phe7-substituted peptides bradykinin antagonist are not substrates for kininase II. Peptides 10:109–112

    Google Scholar 

  • Vinegar R, Truax JF, Selph JL, Johnston PR, Venable AL, McKenzie KK (1987) Pathway to carrageenan-induced inflammation in the hind limb of the rat. Fed Proc 46:118–126

    Google Scholar 

  • Wilson DD, de Garavilla L, Kuhn W, Togo J, Burch RM, Steranka LR (1989) D-Arg[Hyp3DPhe7]Bradykinin, a bradykinin antagonist, decreases mortality in a rat model of endotoxic shock. Circ Shock 27:93–101

    Google Scholar 

  • Whalley ET, Nwator IA, Stewart JM, Vavrek RJ (1987) Analysis of the receptors mediating vascular actions of bradykinin. Naunyn-Schmiedeberg's Arch Pharmacol 336:430–433

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Send offprint requests to R. M. Burch at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burch, R.M., DeHaas, C. A bradykinin antagonist inhibits carrageenan edema in rats. Naunyn-Schmiedeberg's Arch Pharmacol 342, 189–193 (1990). https://doi.org/10.1007/BF00166963

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00166963

Key words

Navigation