Kinin–kallikrein system
The kinin–kallikrein system or simply kinin system is a poorly understood
History
The system was discovered in 1909 when researchers discovered that injection with urine (high in kinins) led to hypotension (low blood pressure).[3] The researchers Emil Karl Frey, Heinrich Kraut and Eugen Werle discovered high-molecular weight kininogen in urine around 1930.[4]
Etymology
kinin [Gk] kīn(eîn) to move, set in motion. kallikrein [Gk ] kalli~ sweet and krein = kreos, flesh, named for the pancreatic extracts where it was first discovered[5][citation needed]
Members
The system consists of a number of large proteins, some small
Proteins
- HMWK is produced by the liver together with prekallikrein (see below). It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity.
- LMWK is produced locally by numerous tissues, and secreted together with tissue kallikrein.
Polypeptides
- Bradykinin (BK), which acts on the B2 receptor and slightly on B1, is produced when kallikrein releases it from HMWK. It is a nonapeptide (9 amino acids) with the amino acid sequence Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg.
- Kallidin (KD) is released from LMWK by tissue kallikrein. It is a decapeptide. KD has the same amino acid sequence as Bradykinin with the addition of a Lysine at the N-terminus, thus is sometimes referred to as Lys-Bradykinin.
HMWK and LMWK are formed by alternative splicing of the same gene.[6]
Enzymes
- Kallikreins (tissue and plasma kallikrein) are serine proteases that liberate kinins[7] (BK and KD) from the kininogens, which are plasma proteins that are converted into vasoactive peptides.[8] Prekallikrein is the precursor of plasma kallikrein. It can only activate kinins after being activated itself by factor XIIa or other stimuli.
- Carboxypeptidases are present in two forms: N circulates and M is membrane-bound. They remove arginine residues at the carboxy-terminus of BK and KD.
- Angiotensin converting enzyme (ACE), also termed kininase II, inactivates a number of peptide mediators, including bradykinin. It is better known for activating angiotensin.
- Neutral endopeptidase also deactivates kinins and other mediators.
Pharmacology
Inhibition of ACE with
There are hypotheses that many of the ACE-inhibitors' beneficial effects are due to their influence on the kinin-kallikrein system. This includes their effects in
Role in disease
Defects of the kinin-kallikrein system in diseases are not generally recognized. The system is the subject of much research due to its relationship to the
C1-INH Involvement
C1-inhibitor is a serine protease inhibitor (serpin) protein.
References
- ISBN 978-81-312-1158-8. Retrieved 25 November 2010.
- ISBN 978-3-11-025235-4.
- ^ Abelous JE, Bardier E (1909). "Les substances hypotensives de l'urine humaine normale". CR Soc Biol (in French). 66: 511–20.
- ]
- ^ "Historical Background. The Kallikrein-Kinin System". E. K. Frey – E. Werle Foundation of the Henning L. Voigt Family.
- ^ Goodman & Gilman's Pharmacology; Chapter 24. Histamine, Bradykinin, and Their Antagonists
- ISBN 978-3-540-38916-3. Retrieved 11 December 2010.
- ^ Kumar, V., Abbas, A., Fausto, N. (Editors) Robbins and Cotran pathologic basis of disease. 7th ed. Philadelphia: Elsevier 2005;Page 65.
the live link for your reference is https://www.degruyter.com/document/doi/10.1515/bchm2.1930.189.3-4.97/html
External links
- Kallikrein-Kinin+System at the U.S. National Library of Medicine Medical Subject Headings (MeSH)