The kinin-kallikrein system is a group of blood proteins that play a role in inflammation , controlling blood pressure , coagulation and the occurrence of pain. The most important components of this system are bradykinin and callidine .
Content
History
The system was discovered in 1909 ( Abelous & Bardier ), when scientists found that intravenous administration of urine (rich in kinins ) leads to a decrease in blood pressure) [1] . Scientists Emil Karl Frey , Heinrich Kraut and Eugen Werle discovered high molecular weight kininogen in urine in 1930 [2] .
Composition
The kinin-kallikrein system consists of a group of high molecular weight proteins, small polypeptides, as well as a set of activating and deactivating enzyme components.
Squirrels
High molecular weight kininogen (VMK) and low molecular weight kininogen (NMK) serve as precursors of polypeptides. They themselves do not have activity.
- IUD is synthesized in the liver along with precallicrein . It does not have catalytic activity.
- NMC is synthesized locally, by many tissues, and is secreted together with tissue kallikrein .
IUD and IUD are formed as a result of alternative splicing of a single gene [3] .
Polypeptides
- Bradykinin , acting on B2 and to a lesser extent on B1 receptors, is formed from IUDs under the action of kallikrein. The chemical composition is nonapeptide.
- Callidine is a decapeptide released from NMC when exposed to tissue kallikrein.
Enzymes
- Kallikreins (tissue and plasma) are serine proteases that catalyze the formation of kinins from kininogens [4] . Prekallikrein serves as a precursor to plasma kallikrein. It can catalyze the formation of kinins only after activation by the Hageman factor .
- Carboxypeptidases are present in two forms: a circulating N-form and a membrane-bound M-form.
- Angiotensin-converting enzyme ( ACE or kininase II ) inactivates a group of peptides , including bradykinin. Catalyzes the formation of angiotensin II from angiotensin I.
- Neutral endopeptidase also inactivates kinins.
Pharmacology
ACE inhibitors reduce the concentration of angiotensin II vasoconstrictor, but increase the level of bradykinin. This explains the presence of dry cough in patients taking ACE inhibitors.
Notes
- ↑ Abelous JE, Bardier E. Les substances hypotensives de l'urine humaine normale. CR Soc Biol 1909; 66: 511-20.
- ↑ Kraut H, Frey EK, Werle E. Der Nachweis eines Kreislaufhormon in der Pankreasdrüse. Hoppe-Seylers Z Physiol Chem 1930; 189: 97-106.
- ↑ Goodman & Gilman's Pharmacology; Chapter 24. Histamine, Bradykinin, and Their Antagonists
- ↑ Kumar, V., Abbas, A., Fausto, N. (Editors) Robbins and Cotran pathologic basis of disease. 7the ed. Philadelphia: Elsevier 2005; Page 65.
Literature
- Dendorfer A, Wolfrum S, Dominiak P. Pharmacology and cardiovascular implications of the kinin-kallikrein system. Jpn J Pharmacol 1999; 79: 403-26. PMID 10361880 .
- Skidgel RA, Alhenc-Gelas F, Campbell WB. Relation of cardiovascular signaling by kinins and products of similar converting enzyme systems; prologue: kinins and related systems. New life for old discoveries. Am J Physiol Heart Circ Physiol 2003; 284: H1886-91. PMID 12742820 .