Kallikrein–Kinin System

Abstract

Two similar proteolytic cascades lead to release of bradykinin and Lys‐bradykinin in tissues; these peptides act as autocoids, the first favouring blood clotting and endothelial protection, the second by initiating and maintaining tissue reactions to noxious stimuli. Kinin biological actions are mediated by two different receptor types, the constitutive B2 which promotes initial reactions and the inducible B1 which may later maintain mechanisms of defense and repair.

Key Concepts

  • Kinin–kallikrein system is a hormonal system that plays a major role in inflammation, blood pressure control, coagulation, pain and cellular proliferation.
  • Kinin–kallikrein system involves coagulation factor XII (FXII), the complex of prekallikrein (PK) and high‐molecular‐weight kininogen (HK).
  • Coagulation factor XII, also known as Hageman factor, is a plasma serine protease produced by hepatocytes. Factor XII activates factor XI and prekallikrein.
  • Kallikreins (tissue and plasma kallikrein) are serine proteases that liberate kinins (bradykinin, BK and kallidin, KD) from the kininogens (HK and LK).
  • High‐molecular‐weight kininogen and low‐molecular‐weight kininogen are precursors of the kinins, (HK) is precursor of BK and (LK) is precursor of KD.
  • Bradykinin (BK) is a nonapeptide hormone with sequence Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe‐Arg. BK is produced when kallikrein releases it from HK.
  • Kallidin (KD) has the same amino acid sequence as Bradykinin with the addition of a Lysine at the N‐terminus, thus it is also called Lys‐BK. Kallidin is released from LK by tissue kallikrein.
  • Kinins are potent hypotensive peptide hormones that are also involved in pain, neurotransmission, inflammation and cell proliferation processes.
  • The various physiopathological actions of kinins are mediated by two receptor types, called B1R and B2R, which are G‐protein coupled receptors.

Keywords: kallikreins; kininogens; kinins; B1 and B2 receptors; inflammation

Figure 1. Biosynthesis of kinins within the blood, tissues and other cellular compartments. Abbreviations: HF: Hageman factor; HFa: activated Hageman factor; HMWK: high‐molecular weight kininogen; LMWK: low‐molecular weight kininogen; CPM and CPN: carboxypeptidases M and N; AmM: aminopeptidase M.
Figure 2. Metabolism of kallidin and derivatives by multiple peptidases. Putative sites of cleavage are indicated by arrows.
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Motta, Guacyara, Tersariol, Ivarne LS, Calo, Girolamo, Gobeil, Fernand, and Regoli, Domenico(Dec 2018) Kallikrein–Kinin System. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000905.pub2]