Bradykinin
From Wikipedia, the free encyclopedia
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bradykinin receptor B1
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| Identifiers | |
| Symbol(s) | BDKRB1 |
| Entrez | 623 |
| OMIM | 600337 |
| RefSeq | NM_000710 |
| UniProt | P46663 |
| Other data | |
| Locus | Chr. 14 q32.1-32.2 |
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bradykinin receptor B2
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| Identifiers | |
| Symbol(s) | BDKRB2 |
| Entrez | 624 |
| OMIM | 113503 |
| RefSeq | NM_000623 |
| UniProt | P30411 |
| Other data | |
| Locus | Chr. 14 q32.1-32.2 |
Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids.
Contents |
[edit] Structure
The amino acid sequence of bradykinin is: arg - pro - pro - gly - phe - ser - pro - phe - arg. Its empirical formula is therefore C50H73N15O11.
[edit] Synthesis
The activity of the kinin-kallikrein system makes bradykinin by proteolytic cleavage of its kininogen precursor, high-molecular weight kininogen (HMWK), using the kininogenase enzyme.
[edit] 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][2].
[edit] Physiological role
[edit] 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.
[edit] 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. The B2 receptor is constitutively active and participates in bradykinin's vasodilatory role.
[edit] History
Bradykinin was discovered by three Brazilian physiologists and pharmacologists working at the Instituto de Biologia de São Paulo, in São Paulo city, led by Dr. Maurício Rocha e Silva. Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld they discovered in 1948 its powerful hypotensive effects in animal preparations. Bradykinin was detected in the blood plasma of animals after the addition of venom of Bothrops jararaca (Brazilian lancehead snake), which was brought by Rosenfeld from the Butantan Institute. This 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."
[edit] 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), which has saved many lives since.
[edit] 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;278(4):H1069-74. Fulltext. PMID 10749699.
- ^ Parpura et al., Glutamate-mediated astrocyte−neuron signalling, Nature 1994 Article
