Bradykinin

Bradykinin is an endogenous vasodilator that is also involved in inflammation.^1,2 It is formed from kininogen via cleavage of high molecular weight kininogen (HMWK) by kallikrein or prekallikrein in a Factor XIIa-dependent or -independent manner.³ Bradykinin binds to the bradykinin B₂ receptor (IC₅₀ = 0.54 nM in COS-7 cells expressing the human receptor) and acts as an agonist but does not bind the bradykinin B₁ receptor (K_i = >10,000 nM in HEK293 cells expressing the human receptor).^4,5 It stimulates arachidonic acid release in CHO cells expressing the human bradykinin B₂ receptor (EC₅₀ = 0.7 nM).⁴ Bradykinin (100 nM) induces relaxation of isolated porcine coronary arterial rings precontracted with acetylcholine or phorbol 12,13-dibutyrate .¹ It induces hyperalgesia in mice when administered at a dose of 1 ?g/paw, an effect that can be reversed by the bradykinin B₂ antagonist icatibant .² Plasma levels of bradykinin are increased in patients during an acute attack of angioedema.⁶

1.Weintraub, N.L., Fang, X., Kaduce, T.L., et al.Potentiation of endothelium-dependent relaxation by epoxyeicosatrienoic acidsCirc. Res.81258-267(1997) 2.Ferreira, S.H., Lorenzetti, B.B., and Poole, S.Bradykinin initiates cytokine-mediated inflammatory hyperalgesiaBr. J. Pharmacol.110(3)1227-1231(1993) 3.Joseph, K., Tholanikunnel, B.G., and Kaplan, A.P.Factor XII-independent cleavage of high-molecular-weight kininogen by prekallikrein and inhibition by C1 inhibitorJ. Allergy Clin. Immunol.124(1)143-149(2009) 4.Hess, J.F., Borkowski, J.A., Macneil, T., et al.Differential pharmacology of cloned human and mouse B2 bradykinin receptorsMol. Pharmacol.45(1)1-8(1994) 5.Bastian, S., Loillier, B., Paquet, J.L., et al.Stable expression of human kinin B1 receptor in 293 cells: Pharmacological and functional characterizationBr. J. Pharmacol.122(2)393-399(1997) 6.Nussberger, J., Cugno, M., Amstutz, C., et al.Plasma bradykinin in angio-oedemaLancet351(9117)1693-1697(1998)