Home > Kinin-kallikrein system

1 History

The system was discovered in 1909 (Abelous & Bardier) when researchers discovered that injection with urine (high in kinins) led to hypotension (low blood pressure). The researchers Emil Karl Frey, Heinrich Kraut and Eugen Werle discovered high-molecular weight kininogen in urine around 1930.

2 Members

The system consists of a number of large proteins, some small polypeptides and a group of enzymes that activate and deactivate the compounds.

2.1 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.

2.2 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 with the amino acidIn chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. In biochemistry, this shorter and more general term is frequently used to refer to alpha amino acids: those amino acids in which the amino and carb sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg.
• Kallidin (KD) is released from LMWK by tissue kallikrein. It is a decapeptide.

3 Enzymes

• Kallikrein s liberate kinins (BK and KD) from the kininogens. Prekallikrein is the precursor of plasma kallikrein. It can only activate kinins after being activated itself by factor XIIThe Hageman factor is a plasma protein now usually known as factor XII . It is part of the coagulation cascade and activates factor XI and prekallikrein. It is an enzyme ( EC ) of the serine protease (or serine endopeptidase) class. Hageman factor deficie or other stimuli.
• Carboxypeptidase s are present 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 angiotensinAngiotensinogen angiotensin I and angiotensin II are peptides involved in maintenance of blood volume and pressure. They play an important role in the renin-angiotensin system. Angiotensinogen Angiotensinogen is the precursor molecule, and it is produced.
• Neutral endopeptidase also deactivates kinins and other mediators.

4 Pharmacology

Inhibition of ACE with ACE inhibitorACE inhibitors or inhibitors of A ngiotensin C onverting E nzyme, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in most cases as the drugs of first choice. Clinical use Indications of ACEs leads to a decrease in angiotensin (a vasoconstrictorA vasoconstrictor is any substance that acts to constrict blood vessels, i. make the lumen narrow. Many vasoconstrictors act on specific receptors, such as vasopressin receptors or adrenoreceptors. Vasoconstrictors are also used clinically to increase blo) but also to an increase in bradykinin due to decreased degradation. This explains why some patients of ACEi's develop a dry coughCough is also the name of a band, see Cough (band A cough is a sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs, and usually accompanied by a distinctive sound. A cough is usually i, and some react with angioedema, a dangerous swelling of the head and neck region.

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 arterial hypertension, in ventricular remodeling (after myocardial infarction) and possibly diabetic nephropathy .