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 (Ki = >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 µg/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)