The Kallikrein-Kinin System: Current and Future Pharmacological Targets

• Published in: Journal of Pharmacological Sciences Vol. 99; no. 1; pp. 6 - 38
• Main Authors: Moreau, Marie Eve, Garbacki, Nancy, Molinaro, Giuseppe, Brown, Nancy J., Marceau, François, Adam, Albert
• Format: Journal Article Web Resource
• Language: English
• Published: Japan Elsevier B.V 2005; The Japanese Pharmacological Society; Japanese Pharmacological Soc; Elsevier
• Subjects: Angioedema - drug therapy; Angioedema - genetics; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Aprotinin - pharmacology; Aprotinin - therapeutic use; B-1 and B-2 receptors; B1 and B2 receptors; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Bradykinin - therapeutic use; Bradykinin B2 Receptor Antagonists; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Complement C1 Inactivator Proteins - deficiency; Complement C1 Inactivator Proteins - genetics; Complement C1 Inhibitor Protein; Human health sciences; Humans; Inflammation - drug therapy; Inflammation - genetics; kallikrein-kinin system; Kallikrein-Kinin System - drug effects; Kallikrein-Kinin System - genetics; Kallikrein-Kinin System - physiology; Kallikreins - antagonists & inhibitors; Kallikreins - metabolism; Kidney Diseases - drug therapy; Kidney Diseases - genetics; Kinins - agonists; Kinins - antagonists & inhibitors; Kinins - metabolism; metallopeptidase; Neprilysin - antagonists & inhibitors; Neprilysin - metabolism; Peptidyl-Dipeptidase A - metabolism; Pharmacie, pharmacologie & toxicologie; pharmacological agent; Pharmacy, pharmacology & toxicology; Polymorphism, Genetic; Pyridines - pharmacology; Pyridines - therapeutic use; Randomized Controlled Trials as Topic; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B1 - metabolism; Receptor, Bradykinin B2 - genetics; Receptor, Bradykinin B2 - metabolism; Sciences de la santé humaine; Serpins - deficiency; Serpins - genetics; Thiazepines - pharmacology; Thiazepines - therapeutic use; kallikrein-kinin system; metallopeptidase; B1 and B2 receptors; pharmacological agent
• ISSN: 1347-8613; 1347-8648; 1347-8648
• DOI: 10.1254/jphs.SRJ05001X

The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.