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14-September-2008 18:02:39 - Bradykinin Bradykinin Identifiers CAS number 58-82-2 PubChem 6026 MeSH Bradykinin 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 references Bradykinin is a peptide that causes blood vessels to enlarge dilate, and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin. Bradykinin works on blood vessels through the release of prostacyclin, nitric oxide, and endothelial-derived hyperpolarizing factor. Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. Contents 1 Structure 2 Synthesis 3 Metabolism 4 Physiological Role Function 4.1 Effects 4.2 Receptors 5 History 6 Therapeutic Implications 7 References 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 or HK, by the enzyme kallikrein. 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 12. Physiological Role Function 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.3 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. Overactivation of bradykinin is thought to play a role in a rare disease called Herary Angioedema, also known as Herary Angio-Neurotic Edema. 4 Receptors The B1 receptor also called bradykinin receptor B1 is expressed only 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. 5. 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. 6 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. Therapeutic Implications 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. Currently, bradykinin inhibitors, also known as antagonists, are being developed as potential therapies for herary angioedema. Icatibant is one such inhibitor. Additional bradykinin inhibitors exist. It has long been known in animal studies that bromelain, a substance obtained from the stems and leaves of the pineapple plant, suppresses trauma-induced swelling caused by the release of bradykinin into the bloodstream and tissues. 7 Other substances that act as bradykinin inhibitors include aloe 8 9 and polyphenols, substances found in red wine and green tea. 10 References ^ Dendorfer A, Wolfrum S, Wagemann M, Qadri F, Dominiak P. Pathways of bradykinin degradation in blood and plasma of normotensive and hypertensive rats. Am J Physiol Heart Circ Physiol 2001;280:H2182-8. Fulltext. PMID 11299220. ^ Kuoppala A, Lindstedt KA, Saarinen J, Kovanen PT, Kokkonen JO. Inactivation of bradykinin by angiotensin-converting enzyme and by carboxypeptidase N in human plasma. Am J Physiol Heart Circ Physiol 2000;2784:H1069-74. Fulltext. PMID 10749699. ^ Parpura et al., Glutamate-mediated astrocyte-neuron signalling, Nature 1994 Article ^ Bas M, Adams V, Suvorava T, Niehues T, Hoffmann TK, Kojda G. Nonallergic angioedema: role of bradykinin. Allergy. 2007 Aug;628:842-56. ^ Peter G. McLean et al., Association between Kinin B1 Receptor Expression and Leukocyte Trafficking across Mouse Mesenteric Postcapillary Venules, The Journal of Experimental Medicine 2000 Article ^ J Duchene et al., A Novel Inflammatory Pathway Involved in Leukocyte Recruitment: Role for the Kinin B1 Receptor and the Chemokine CXCL5, The Journal of Immunology 2007 1 ^ Lotz-Winter H. On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects. Planta Med. 1990 Jun;563:249-53. ^ Bautista-Pérez R, Segura-Cobos D, Vázquez-Cruz B. In vitro antibradykinin activity of Aloe barbadensis gel. J Ethnopharmacol. 2004 Jul;931:89-92. ^ Yagi A, Harada N, Yamada H, Iwadare S, Nishioka I. Antibradykinin active material in Aloe saponaria. J Pharm Sci. 1982 Oct;7110:1172-4. ^ Richard T, Delaunay JC, Mérillon JM, Monti JP. Is the C-terminal region of bradykinin the binding site of polyphenols? J Biomol Struct Dyn. 2003 Dec;213:379-85. v d e 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 v d e Autacoids: kinins Kininogen MHWK, LHWK - Bradykinin Kallidin - Tachykinin - Urotensin 2 Retrieved from http://en..org/wiki/Bradykinin Categories: Peptide hormones | Kinin system Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Français Italiano 日本語 Polski Português Suomi Tiếng Việt Türkçe This page was last modified on 10 September 2008, at 13:34
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