Thekinin–kallikrein system or simplykinin system is a poorly understoodhormonal system with limited available research.^[1] It consists of bloodproteins that play a role ininflammation,^[2]blood pressure control,coagulation andpain. Its important mediatorsbradykinin andkallidin arevasodilators and act on many cell types. Clinical symptoms include marked weakness, tachycardia, fever, leukocytosis. It can also increaseerythrocyte sedimentation rate.

The system was discovered in 1909 when researchers discovered that injection withurine (high in kinins) led tohypotension (low blood pressure).^[3] The researchersEmil Karl Frey,Heinrich Kraut andEugen Werle discovered high-molecular weightkininogen in urine around 1930.^[4]

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]}

The system consists of a number of large proteins, some smallpolypeptides and a group of enzymes that activate and deactivate the compounds.^{[citation needed]}

High-molecular weight kininogen (HMWK) andlow-molecular weight kininogen (LMWK) are precursors of the polypeptides. They have no activity of themselves.^{[citation needed]}

• 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.

• 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 theamino 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]

• 

  Kallikreins (tissue and plasma kallikrein) areserine proteases that liberate kinins^[7] (BK and KD) from thekininogens, which are plasma proteins that are converted intovasoactive peptides.^[8]Prekallikrein is the precursor of plasma kallikrein. It can only activate kinins after being activated itself byfactor XIIa or other stimuli.
• Carboxypeptidases are present in two forms: N circulates and M is membrane-bound. They removearginine residues at thecarboxy-terminus of BK and KD.
• Angiotensin converting enzyme (ACE), also termedkininase II, inactivates a number of peptide mediators, includingbradykinin. It is better known for activatingangiotensin.
• Neutral endopeptidase also deactivates kinins and other mediators.

Inhibition of ACE withACE inhibitors leads to decreased conversion of angiotensin I to angiotensin II (avasoconstrictor) but also to an increase in bradykinin due to decreased degradation. This explains why some patients taking ACE inhibitors develop a dry cough, and some react withangioedema, a dangerous swelling of the head and neck region.^{[citation needed]}

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 inarterial hypertension, inventricular remodeling (after myocardial infarction) and possiblydiabetic nephropathy.^{[citation needed]}

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 theinflammation andblood pressure systems. It is known that kinins are inflammatory mediators that cause dilation of blood vessels and increased vascular permeability. Kinins are small peptides produced from kininogen by kallikrein and are broken down by kininases. They act onphospholipase and increasearachidonic acid release and thus prostaglandin (PGE2) production.^{[citation needed]}

C1-inhibitor is a serine protease inhibitor (serpin) protein.C1-INH is the most important physiological inhibitor of plasma kallikrein, fXIa and fXIIa. C1-INH also inhibits proteinases of the fibrinolytic, clotting, and kinin pathways. Deficiency of C1-INH permits plasma kallikrein activation, which leads to the production of the vasoactive peptide bradykinin.^{[citation needed]}

the live link for your reference ishttps://www.degruyter.com/document/doi/10.1515/bchm2.1930.189.3-4.97/html

• Kallikrein-Kinin+System at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Kinin–kallikrein system
• Cardiovascular physiology

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