Bradykinin
| Bradykinin | ||
|---|---|---|
|
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| Properties of human protein | ||
| Mass / length primary structure | 9 amino acids | |
| Precursor | Kininogen-1 (626 aa) | |
| Identifier | ||
| Gene name | KNG1 | |
| External IDs | ||
Bradykinin is a peptide and tissue hormone belonging to the Kinin group. It is a vasoactive one , i.e. H. Blood vessel-altering oligopeptide that consists of nine amino acids and has a similar effect to histamine . In the case of inflammation or injuries, it is involved in increasing the sensitivity to pain in the affected part of the body.
As a result of its specific binding to receptors in the vascular endothelium, it causes a change in the tone of the smooth muscles (depending on the site of action), increases the permeability of the vessel and causes pain.
structure
The primary structure of bradykinin consists of 9 amino acid residues (H 2 N- Arg - Pro - Pro - Gly - Phe - Ser - Pro - Phe - Arg -COOH) with the empirical formula C 50 H 73 N 15 O 11 and a molecular weight of 1060.22 Da .
synthesis
Bradykinin is released from its inactive precursor proteins, the kininogens, by kininogenases such as kallikrein . Through the activity of the kinin-kallikrein system , bradykinin is formed by proteolytic cleavage of its kininogen precursor protein high molecular weight kininogen (HMW-kininogen) with the aid of the enzyme kininogenase.
metabolism
The kinins are inactivated by splitting off C-terminal dipeptides using peptidyl dipeptidase, an enzyme that is identical to the angiotensin-converting enzyme (ACE) of the renin-angiotensin-aldosterone system .
In humans, bradykinin is broken down by various enzymes: the angiotensin converting enzyme (ACE), aminopeptidase P (APP), carboxypeptidase N (CPN) and neprilysin , which are in positions 7-8, 1-2, 8-9 and 7, respectively -8 columns.
Physiological role
Receptors
In mammals there are two types of bradykinin receptors known. The B 1 receptor is only expressed as a result of tissue damage and is believed to play a role in chronic pain. The B 2 receptor is constitutively active and contributes to the vasodilating effect of bradykinin.
Effects
Bradykinin is a potent endothelium- dependent vasodilator , causes contraction of non-vascular smooth muscle cells , increases vascular permeability and is also involved in the mechanism of pain . In some ways it has similar effects to histamine, and like histamine, it is released primarily from venules rather than arterioles .
Bradykinin increases intracellular calcium levels in neocortical astrocytes and causes them to release glutamate .
Bradykinin is also believed to be the cause of dry coughs in some patients on ACE inhibitor therapy . This refractory cough is a common cause of needing to discontinue ACE inhibitor therapy.
Functions of bradykinin
- Participation in the generation of pain
- Involvement in allergic and anaphylactic reactions
- Mediator of angioedema (e.g. hereditary angioedema )
- Mediator of inflammation (similar to: histamine)
- Vasodilation
- Contraction of the bronchial , intestinal and uterine muscles
- Increase in vascular permeability
- Chemotactic effect on leukocytes
Poisons from the stinging voices (e.g. bee venom ) mostly contain bradykinin.
history
Bradykinin was discovered by three Brazilian physiologists and pharmacologists who worked at the Instituto de Biologia de São Paulo, in São Paulo, under the direction of Maurício Rocha e Silva . Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, he discovered its strong hypotensive effects in animal models in 1948 . Bradykinin was discovered in the blood plasma of animals after the addition of Venom from Bothrops jararaca (Jararaca lance viper), which was provided by Rosenfeld from the Butantan Institute . This discovery was part of an ongoing study into circulatory shock and proteolytic enzymes linked to the toxicology of snake bites that Rocha e Silva began in 1939. Bradykinin should prove to be a new autopharmacological principle, that is, as a substance that is released in the body via a metabolic modification from precursor substances that are pharmacologically active. According to BJ Hagwood, Rocha e Silva's biographer, "The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena, including circulatory shock induced by venomas and toxins ."
The practical significance of the discovery of bradykinin became apparent when one of his staff at the Faculty of Medicine of Ribeirão Preto at the University of São Paulo, Sérgio Henrique Ferreira , discovered a bradykinin potentiating factor (BPF) in the venom of Bothrops that had both duration as well as the extent of the effects of bradykinin on vasodilation and the subsequent drop in blood pressure . Based on this finding, researchers at BMS developed the first of a new generation of highly effective antihypertensive drugs, so-called ACE inhibitors such as captopril .
Individual evidence
- ↑ UniProt P01042
- ↑ A. Dendorfer, S. Wolfrum, M. Wagemann, F. Qadri, P. Dominiak: Pathways of bradykinin degradation in blood and plasma of normotensive and hypertensive rats. ( Memento of the original from November 14, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Am J Physiol Heart Circ Physiol. 280, 2001, pp. H2182-H2188. PMID 11299220 .
- ↑ A. Kuoppala, KA Lindstedt, J. Saarinen, PT Kovanen, JO Kokkonen: Inactivation of bradykinin by angiotensin-converting enzyme and by carboxypeptidase N in human plasma. ( Memento of the original from June 1, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: Am J Physiol Heart Circ Physiol. 278 (4), 2000, pp. H1069-H1074. PMID 10749699 .
- ↑ Vladimir Parpura, Trent A. Basarsky et al. a .: Glutamate-mediated astrocyte-neuron signaling. In: Nature. 369, 1994, p. 744, doi: 10.1038 / 369744a0 .
