Cited by 457Coagulation, Bradykinin, Polyphosphates, and AngioedemaPineapple and bromelain studiesComplement system in diseases

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

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Moreau, Marie Eve, Garbacki, Nancy, Molinaro, Giuseppe, Brown, Nancy J., Marceau, François, Adam, Albert·2005·Journal of Pharmacological Sciences

Abstract

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.

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Crossref · 10.1254/jphs.srj05001x

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327 of 327 references verified0 citation errors · 0 not checkable

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  • When ACE is inhibited, aminopeptidase P (APP) is the main enzyme that inactivates bradykinin.

    “During ACE inhibition, bradykinin is primarily inactivated by aminopeptidase P (APP).”

    From Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema (2010) · cites this paper as [8]

    Section 3.3 (page not available) says APP inactivates bradykinin in human plasma, but identifies it as the major inactivation pathway for des-Arg9-bradykinin, not bradykinin itself. The paper does not establish that APP becomes the primary enzyme inactivating bradykinin during ACE inhibition. (LLM, conf=0.88)

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Research works printed but not linked: 9

  1. [1]1. Abelous J, Bardier E. Les substances hypotensives de l'urine humaine normale. CR Soc Biol. 1909;66:511-512. (in French)
  2. [143]143. - N-isopropyl-N-methylpropanamide hydrochloride], a new non- peptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization. J Pharmacol Exp Ther. 2004;309:661-669. 144
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Authors
Moreau, M. E., Garbacki, N., Molinaro, G., Brown, N. J., Marceau, F., & Adam, A.
Affiliations
  • Université de Montréal (CA)
  • University of Liège (BE)
  • Vanderbilt University (US)
  • Centre hospitalier universitaire de Québec (CA)
Venue
Journal of Pharmacological Sciences
Published
2005
Volume
99
Issue
1
Pages
6-38
ISSN
  • 1347-8613 (ISSN-L)
  • 1347-8648
OpenAlex
W1967632907
Cited by
457
References
327
Citations by year
2026: 2 · 2025: 9 · 2024: 19 · 2023: 14 · 2022: 7 · 2021: 20 · 2020: 24 · 2019: 9 · 2018: 20 · 2017: 13 · 2016: 29 · 2015: 23 · 2014: 24 · 2013: 37 · 2012: 33
FWCI
4.07
Type
journal article
Language
en
Open access
Locations
  • Journal of Pharmacological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ORBi (University of Liège) (submittedVersion, other-oa)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL079184)
Topics
  • Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Keywords
kallikrein-kinin system, bradykinin, kininogen, tissue kallikrein, plasma kallikrein, kinin receptors, metalloproteinases, antiproteases, serpins, pro-inflammatory effects, cardioprotection, renin-angiotensin system, coagulation, complement system, therapeutic target
MeSH terms
Angioedema, Angiotensin-Converting Enzyme Inhibitors, Animals, Bradykinin, Cardiovascular Diseases, Complement C1 Inactivator Proteins, Humans, Inflammation, Kallikreins, Aprotinin, Kidney Diseases, Peptidyl-Dipeptidase A, Kinins, Polymorphism, Genetic, Pyridines, Thiazepines, Neprilysin, Serpins, Randomized Controlled Trials as Topic, Kallikrein-Kinin System, Receptor, Bradykinin B2, Receptor, Bradykinin B1, Complement C1 Inhibitor Protein, Bradykinin B2 Receptor Antagonists

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