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bradykinin

What is bradykinin?

Bradykinin is a hormone, that is, it contributes to the communication of cells with each other. It has a similar effect as histamine. In contrast to steroid hormones such as cortisol, it is composed of juxtaposed amino acids, in this case there are 9 different amino acids. The biological half-life is just 15 seconds. Bradykinin is one of the kinins that are tissue hormones, so not systemic in the whole body, but act locally. Especially in the inflammatory process bradykinin plays an important role by expanding the nearby arteries and veins, so that white blood cells can penetrate into the inflamed area to ward off pathogens. In addition, bradykinin increases the sensation of pain in the inflamed area.

Task, function and effects of bradykinin

The main task of bradykinin is to contribute to the development of inflammation in an injured area. This is necessary in order to enable a quick healing and to fight possibly occurring pathogens in the best possible way. In the case of an injury, a special hormone receptor (B2 receptor) is built into the cell walls of nearby blood vessels, to which the bradykinin specifically binds. This bond leads to a relaxation of the vascular musculature and thus to an extension. As a result, the local blood pressure drops, but at the same time there is an increased blood flow, which manifests itself in a reddening and an elevated temperature. In addition, the permeability of the vessel wall increases, whereby white blood cells reach the injured area to ward off intruders. In addition, it has a mobility-enhancing effect on these blood cells so that they can move better through the connective tissue. In addition, fluid escapes from the vessel into the tissue, causing the swelling of inflammation. In addition, bradykinin binds to another hormone receptor (B1 receptor), which is formed by injured tissue, thereby locally increasing pain sensation. For this reason, inflamed skin areas are particularly sensitive to pain or even pain without irritation.

In addition to these easy-to-identify effects, bradykinin has a few other effects as well. For example, it causes a constriction of the bronchi by stimulating the bronchial muscles. If this happens excessively, it can lead to dry coughing.

Bradykinin also causes smooth muscle contraction in the gastrointestinal tract and uterus. In the kidney, bradykinin causes increased diuresis (urine production) with loss of sodium. Bradykinin also plays a role in blood coagulation: it is activated by factor XII from the coagulation cascade and contributes to the release of the tissue plasminogen activator, which activates the enzyme plasmin. This ensures that a thrombus is degraded again after fulfilling its function.

Due to its blood vessel dilating effect, it also plays a role in temperature regulation when excreted in sweat: A widened vessel releases more heat to the outside world than through a narrowly positioned one.

Even in allergic reactions bradykinin plays a role, by actually harmless foreign substances are perceived as dangerous and z. B. cause the constriction of bronchi or swelling of the skin.

Bradykinin is degraded by various enzymes contained in the blood.

What is the bradykinin antagonist?

Recently, Icatibant as a bradykinin antagonist (antagonist) is available for the treatment of hereditary angioedema. This artificially produced active substance can be injected under the skin in an acute attack in dissolved form with the aid of a syringe and leads to an improvement of the symptoms after 1-2 hours. At the molecular level, the antagonist binds to and blocks the vascular B2 receptor, preventing bradykinin binding and activation of the receptor. This principle is called competitive inhibition. As a result, a vasodilation and an increase in the permeability of the vessel wall is prevented and there is no leakage of liquid. As a result, an otherwise occurring swelling of the affected area remains.

The same mechanism could make Icatibant an effective drug for ascites that commonly occurs in severe liver damage. In this disease, as a result of decreased liver performance and the associated declining oncotic pressure in the blood vessels, more water enters the abdomen, which could possibly be prevented by icatibant.

Icatibant can also be used in some other diseases, especially as an anti-inflammatory agent for chronic inflammatory diseases or vascular diseases.

What role does bradykinin play in angioedema?

Angioedema is a temporary painless swelling of the skin and subcutaneous fatty tissue. It can occur all over the body and remains symptom free in most cases. Angioedema can be problematic in the intestinal area, as these may cause severe pain and can restrict digestion. Particularly dangerous are angioedema in the respiratory tract, as they can block them. In this case, sometimes emergency medical help is needed. The development of angioedema can have very different causes, from allergic reactions to drug intolerance.

A particular form of angioedema is hereditary angioedema (HAE), in which there is a congenital deficiency of C1-esterase inhibitor. As a result, the hormone bradykinin can no longer be broken down so well. As a result, bradykinin influx results in increased fluid outflow from blood vessels, increasing the risk of angioedema. Patients with HAE have a 50% chance of developing dangerous angioedema at least once in their lives. A bradykinin antagonist in syringe form is available for the treatment of HAE.

cough

When taking ACE inhibitors (drugs that are used primarily for high blood pressure) may cause a dry cough. The reason for this is that the hormone bradykinin is degraded by ACE (Angiotensin Converting Enzyme), among others, and is therefore increased in the body when it is inhibited by this enzyme. On the bronchi, bradykinin causes smooth muscle contraction and constriction of the airways, which in some cases can lead to uncomfortable, dry coughing. This can lead to the therapy with ACE inhibitors must be discontinued.

What does Bradykinin have to do with Kallikrein?

Many kinins are present in the blood in their (partially) inactive precursor and must be activated by the enzyme kallikrein in order to be able to exert their effect. For example, bradykininogen (inactive precursor) must first cleave an amino acid through kallikrein. This is a serine, which makes kallikrein a serine protease (SERP). This process plays an important role in inflammatory processes and coagulation activation.

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