Bradykinin
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| Bradykinin | |
|---|---|
| Image:Bradykinin.png | |
| Identifiers | |
| CAS number | |
| PubChem | |
| MeSH | |
| Properties | |
| Molecular formula | C50H73N15O11 |
| Molar mass | 1060.21 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references | |
Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids.
Structure
Bradykinin is a 9 amino acid peptide chain. The amino acid sequence of bradykinin is: Arg - Pro - Pro - Gly - Phe - Ser - Pro - Phe - Arg. Its empirical formula is therefore C50H73N15O11.
Synthesis
The kinin-kallikrein system makes bradykinin by proteolytic cleavage of its kininogen precursor, high-molecular weight kininogen (HMWK), by the enzyme kallikrein. ACE inhibitors prevent ACE (angiotensin converting enzyme) from degrading bradykinin, which accumulates in the lungs and acts as an irritant and provokes coughing.
Metabolism
In humans, bradykinin is broken down by three kininases: angiotensin-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N (CPN), which cleave the 7-8, 1-2, and 8-9 positions, respectively [1][1].
Physiological role
Effects
Bradykinin is a potent endothelium-dependent vasodilator, causes contraction of non-vascular smooth muscle, increases vascular permeability and also is involved in the mechanism of pain. In some aspects, it has similar actions to that of histamine, and like histamine is released from venules rather than arterioles.
Bradykinin raises internal calcium levels in neocortical astrocytes causing them to release glutamate.[1]
Bradykinin is also thought to be the cause of the dry cough in some patients on angiotensin converting enzyme (ACE) inhibitor drugs. This refractory cough is a common cause for stopping ACE-inhibitor therapy.
Receptors
In mammals, two types of bradykinin receptors are known:
- The B1 receptor is only expressed as a result of tissue injury, and is presumed to play a role in chronic pain. This receptor has been also described to play a role in inflammation. [1]. Most recently, it has been shown that the kinin B1 receptor recruits neutrophil via the chemokine CXCL5 production. Moreover, endothelial cells have been described as a potential source for this B1 receptor-CXCL5 pathway. [1]
- The B2 receptor is constitutively active and participates in bradykinin's vasodilatory role.
The kinin B1 and B2 receptors belong to G protein coupled receptor (GPCR) family.
History
Bradykinin was discovered in 1948 by three Brazilian physiologists and pharmacologists working at the Instituto Biológico, in São Paulo, Brazil, led by Dr. Maurício Rocha e Silva. Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, they discovered the powerful hypotensive effects of bradykinin in animal preparations. Bradykinin was detected in the blood plasma of animals after the addition of venom extracted from the Bothrops jararaca (Brazilian lancehead snake), brought by Rosenfeld from the Butantan Institute. The discovery was part of a continuing study on circulatory shock and proteolytic enzymes related to the toxicology of snake bites, started by Rocha e Silva as early as 1939. Bradykinin was to prove a new autopharmacological principle, i.e., a substance that is released in the body by a metabolic modification from precursors, which are pharmacologically active. According to B.J. 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 venoms and toxins."
Applications
The practical importance of the discovery of bradykinin became apparent when one of his collaborators at the Medical School of Ribeirão Preto at the University of São Paulo, Dr. Sérgio Henrique Ferreira, discovered a bradykinin potentiating factor (BPF) in the bothropic venom which increases powerfully both the duration and magnitude of its effects on vasodilation and the consequent fall in blood pressure. On the basis of this finding, Squibb scientists developed the first of a new generation of highly-effective anti-hypertensive drugs, the so-called ACE inhibitors, such as captopril (trademarked Capoten).
References
Peptides: neuropeptides | |
|---|---|
| Hypothalamic | Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC (ACTH, MSH, Lipotropin) |
| Gastrointestinal hormones | Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide |
| Other hormones | Vasopressin - Calcitonin - |
| Other | Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins (Bradykinin, Tachykinins ) - Neuromedin (B, N, U) - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide |
Autacoids: kinins |
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| Kininogen (MHWK, LHWK) - Bradykinin (Kallidin) - Tachykinin - Urotensin 2 |
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 .
