Kinin

Kinins are to the tissue hormones scoring biologically active oligopeptides, they are of kallikrein from kininogens ( inactive precursor of kinins ) are released. The kinin - kallikrein system or simply kinin system is a poorly marginated system of blood proteins that plays a role in inflammation, blood pressure control, coagulation and pain. Its important mediators bradykinin and kallidin are vasodilators and act on many cell types.

Physiological significance

  • Kinins may be responsible for the activity of smooth muscle organs.
  • They regulate the vessel length and vessel permeability.
  • They influence the excitation of sensitive structures ( pain).
  • They are involved in the development of shock and inflammation.

Role in disease

Disorders of the kinin - kallikrein system in diseases generally are not sufficiently clarified. The system is the subject of extensive research due to its association with the inflammatory and blood pressure systems.

History

The system was discovered in 1909 ( Abelous & Bardier ), noted researcher, that an injection of urine ( high Kiningehalt ) to hypotension (low blood pressure) led. The researchers Emil Karl Frey, Heinrich Kraut and Eugen Werle discovered high molecular weight kininogen in the urine about 1930.

Members

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

The following kinins are known

  • Bradykinin
  • Lysylbradykinin
  • Harnkinin
  • Neurokinin
  • Kolostkinin

Proteins

High molecular weight kininogen (HMW kininogen ) and low molecular weight kininogen ( LMW kininogen ) are precursors of the polypeptides. They have an effect per se.

  • HMW kininogen is used by the liver, together with prekallikrein (see below ) are formed. It mainly acts as a cofactor for coagulation and inflammation and has no intrinsic catalytic activity.
  • LMW kininogen is locally formed by numerous tissues and secreted together with tissue kallikrein.

Polypeptides

  • Bradykinin (BK), which acts on the B2 receptor and slightly also in the B1- receptor is produced, when it releases from the kallikrein - kininogen HMW. It is a nonapeptide with the amino acid sequence Arg -Pro-Pro -Gly -Phe- Ser-Pro -Phe -Arg.
  • Kallidin (KD) is released by tissue kallikrein from LMW kininogen. It is a decapeptide.

Enzymes

  • Kallikreins ( tissue and plasma kallikrein ) are serine proteases which liberate kinins (BK and KD) from kininogens. Prekallikrein is the precursor of plasma kallikrein. It can kinins activate only after it was itself activated by factor XII or other stimuli.
  • Carboxypeptidases are present in two forms: N circulates and M is membrane-bound. Remove arginine residues at the carboxy -terminal end of BK and KD.
  • Angiotensin converting enzyme ( ACE), also known as kininase II, inactivates a number of peptide mediators, including bradykinin. It is better known because of the activation of angiotensin.
  • Neutral endopeptidase also disabled kinins and other mediators.

Pharmacology

Inhibition of ACE with ACE inhibitors leads to a decrease of angiotensin ( a vasoconstrictor ), but also to an increase of bradykinin due to a reduced degradation. This explains why some patients on therapy with ACE inhibitors develop a dry cough, and some react with a angioedema, a dangerous swelling of the head and neck region.

There are hypotheses, according to which many of the beneficial effects of ACE inhibitors based on their effect on the kinin - kallikrein system. This includes their effects in arterial hypertension, the ventricular remodeling ( after myocardial infarction ), and possibly in diabetic nephropathy.

Degradation and synthesis of kinins

  • Degradation:

The Kininfreisetzung is inhibited by aprotinin.

  • Physical synthesis:

Kinin is metabolized by proteolytic degradation of bradykinin to other kinins ( by kininase II).

Hemostasis
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