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 B 2 which promotes initial reactions and the inducible B 1 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 B 1 R and B 2 R, which are G‐protein coupled receptors.

Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond

“…Recently, comprehensive reviews have extensively dealt with many aspects of BK and desArg 9 BK generation; its metabolism by endo, carboxy, and amino peptidases; and the multitude of actions attributed to both peptides in many cell models, tissues, and organs ( Lalmanach et al, 2010 ; Campbell, 2013 ; Motta et al, 2018 ). The role of BK in angioedema as the B2BK receptor agonist has been unequivocally established ( Hofman et al, 2016 ; Schmaeir, 2018 ; Rex et al, 2022 ; Gailani, 2023 ) through the increase in vascular permeability, but also desArg 9 BK, the B1BK receptor agonist, seems to be relevant as these receptors modulate neutrophil trafficking ( Araújo et al, 2001 ).…”

Dabsylated Bradykinin Is Cleaved by Snake Venom Proteases from Echis ocellatus

“…The substrates sharing at least two consecutive amino acids with BK are given in the Supplementary Excel file (JPT table ). The substrate of most resemblance to BK was SPFRSSRI derived from human kininogen-1 (KNG1; incidentally, the precursor of BK within the kinin-kallikrein system [40]) sharing the SPFR sequence unit. Six substrates of the JPT kit had three successive amino acids in common with BK (RPP, PPG) and 20 shared two residues (RP, PG, FS).…”