An endogenous vasodilator
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 ?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)
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Cell experiment: |
SW480 cells are pretreated with different concentrations of bradykinin (0, 0.1, 0.5, 1 μM), and then subjected to invasion and migration assays[2]. |
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Animal experiment: |
Rats: Bradykinin acetate is applied topically to the surface of the ovary with a thin piece of cotton (7×7 mm square) soaked with the solution. After application for 30 s, the cotton is removed. Each of the stimuli is delivered to the animal after observing stabilization of heart rate and mean arterial pressure[4]. Mouse: Mice are randomly divided into 3 groups: Sham, Model and Bradykinin. Before surgical procedure, the mice of bradykinin group are intraperitoneally injected with bradykinin (10 mg/kg/d) once a day for three days. After ligation, the mice receive bradykinin injection for another two days and analgesic therapy is performed using buprenorphine at 0.1 mg/kg body weight for 3 days. The mice in other groups receive equal saline as control[3]. |
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参考文献: [1]. Hornig B, et al. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors inhumans. Circulation. 1997 Mar 4;95(5):1115-8. |
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