The kallikrein-kinin system: current and future pharmacological targets.
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.
Moreau
Marie Eve
ME
Faculty of Pharmacy, University of Montreal, Canada.
Garbacki
Nancy
N
Molinaro
Giuseppe
G
Brown
Nancy J
NJ
Marceau
François
F
Adam
Albert
A
D000799:Angioedema / Q000188:drug therapy / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology / Q000627:therapeutic use; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency / Q000235:genetics; D050718:Complement C1 Inhibitor Protein; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007674:Kidney Diseases / Q000188:drug therapy / Q000235:genetics; D007705:Kinins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011110:Polymorphism, Genetic; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000172:deficiency / Q000235:genetics; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D007705:Kinins; D011725:Pyridines; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C469952:SERPING1 protein, human; D015843:Serpins; D013841:Thiazepines; C106266:omapatrilat; C065679:icatibant; D007611:Aprotinin; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D015260:Neprilysin; D001920:Bradykinin