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.
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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)
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
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
Farmer SG, Burch RM (1990) Pharmacology of bradykinin antagonists. In: Burch RM (ed) Bradykinin antagonists: basic and clinical research, Dekker, New York (in press)
Farmer SG, Burch RM, Meeker SA, Wilkins DE (1989) Evidence for a pulmonary B3 bradykinin receptor. Mol Pharmacol 36:1–8
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
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
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
Regoli D, Barabe (1980) Pharmacology of bradykinin and related kinins. Pharmacol Rev 32:1–46
Spragg J, Vavrek RJ, Stewart JM (1988) The inhibition of glandular kallikrein by peptide analog antagonists of bradykinin. Peptides 9:203–206
Steranka LR, Rodriguez R, DeHaas CJ (1988) Effects of bradykinin antagonists on vascular permeability in rat skin. Pharmacologist 30:A30
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)
Tiffany CW, Burch RM (1989) Bradykinin stimulates tumor necrosis factor and interleukin 1 release from macrophages. FEBS Lett 247:189–192
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
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
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
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
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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
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DOI: https://doi.org/10.1007/BF00166963