Bradykinin|58-82-2|安捷凯

Background

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)

Protocol

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].

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].

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.
[2]. Wang G, et al. Bradykinin stimulates IL-6 production and cell invasion in colorectal cancer cells. Oncol Rep. 2014 Oct;32(4):1709-14.
[3]. Dong R, et al. Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway. Cell Physiol Biochem. 2015;37(4):1592-606.
[4]. Uchida S, et al. Afferent fibers involved in the bradykinin-induced cardiovascular reflexes from the ovary in rats. Auton Neurosci. 2015 Dec;193:57-62.
[5]. Liu LT, et al. Effect of vascular bradykinin on pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis. Eur Rev Med Pharmacol Sci. 2015;19(14):2646-50.

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Bradykinin

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Background

Protocol

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