Kinin-kallikrein system
You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884
Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
The kinin-kallikrein system or simply kinin system is a poorly delineated 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.
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).[1] The researchers Emil Karl Frey, Heinrich Kraut and Eugen Werle discovered high-molecular weight kininogen in urine around 1930.[1]
Members
The system consists of a number of large proteins, some small polypeptides and a group of enzymes that activate and deactivate the compounds.
Proteins
High-molecular weight kininogen (HMWK) and low-molecular weight kininogen (LMWK) are precursors of the polypeptides. They have activity of themselves.
- 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 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 aa 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.[1]
Enzymes
- Kallikreins (tissue and plasma kallikrein) are serine proteases that 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 XII or other stimuli.
- Carboxypeptidases 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 angiotensin.
- Neutral endopeptidase also deactivates kinins and other mediators.
Pharmacology
Inhibition of ACE with ACE inhibitors leads to a decrease in angiotensin (a vasoconstrictor) but also to an increase in bradykinin due to decreased degradation. This explains why some patients of ACEi's develop a dry cough, 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.
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 inflammation and blood 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 on phospholipase and increase arachidonic acid release and thus prostaglandin (PGE2) production.
References
- 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 converning enzyme systems; prologue: kinins and related systems. New life for old discoveries. Am J Physiol Heart Circ Physiol 2003;284:H1886-91. PMID 12742820.
External links
Cardiovascular system, physiology: cardiovascular physiology | |
|---|---|
| Volumes | Preload - Afterload - End-systolic volume - End-diastolic volume - Frank-Starling law of the heart |
| Interactions | Cardiac output - Wiggers diagram - Pressure volume diagram |
| Tropism | Chronotropic - Dromotropic - Inotropic |
| Hemodynamics | Baroreflex - Kinin-kallikrein system - Renin-angiotensin system - Vasoconstrictors - Vasodilators - Compliance - Vascular resistance |
| Other | Electrical conduction system of the heart (Cardiac action potential) |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
