Bradykinin

Bradykinin is a peptide and tissue hormone of the kinin group. Is a vasoactive, i.e. blood vessel changing, oligopeptide consisting of nine amino acids, and effect similar to histamine. If there is inflammation or injury, it is involved in pain sensitivity increase to the affected part of the body.

Due to its specific binding to receptors on the vascular endothelium, it causes a Tonusänderung smooth muscle (depending on the site of action ), increases the permeability of the vessel, and causes pain.

Structure

The primary structure of the bradykinin consists of 9 amino acids ( H2N -Arg-Pro -Pro-Gly -Phe- Ser-Pro -Phe -Arg- COOH) with the molecular formula C50H73N15O11, and a molecular mass of 1060.22 Da.

Synthesis

Bradykinin is released by kininogenases as kallikrein from its inactive precursor proteins, the kininogens. Through the activity of the kinin - kallikrein system, bradykinin via a proteolytic cleavage of its kininogen precursor protein high molecular weight kininogen (HMW kininogen ) is formed by the enzyme kininogenase.

Metabolism

Inactivation of kinins is effected by cleaving the C-terminal dipeptides by peptidyl dipeptidase, an enzyme with the angiotensin converting enzyme (ACE) of the renin -angiotensin -aldosterone system is identical.

In humans, bradykinin is degraded by three Kininases: by angiotensin - converting enzyme (ACE ), aminopeptidase P ( APP) and carboxypeptidase N ( CPN), which cleave the positions 7-8, 1-2 and 8-9.

Physiological role

Receptors

In mammals, two types of bradykinin receptors are known. The B1 receptor is expressed only as a result of tissue injury and is believed to play a role in chronic pain. The B2 receptor is constitutively active and contributes to the vasodilator effect of bradykinin in.

Effects

Bradykinin is a potent endothelium -dependent vasodilator, causes a contraction of non- vascular smooth muscle cells, vascular permeability increases (permeability) and is also involved in the mechanism of pain. In some ways, it has effects similar to histamine and histamine as it is released from venules rather than mainly in the arterioles.

Bradykinin increases intracellular calcium levels in neocortical astrocytes and causes release these glutamate.

Bradykinin that is running a therapy with ACE inhibitors also the cause of dry cough in some patients. This refractory cough is a common reason for the need of settling an ACE - inhibitor therapy.

Functions of bradykinin

  • Involvement in pain generation
  • Involvement in allergic and anaphylactic reactions
  • Mediator of angioedema (eg, hereditary angioedema )
  • Mediator of inflammation (similar: histamine)
  • Vasodilatation
  • Contraction of the bronchial, intestinal and uterine musculature
  • Increase in vascular permeability
  • Chemotactic effect on leukocytes

Poisons the Stechimmen (eg bee venom ) containing largely bradykinin.

History

Bradykinin was discovered by three Brazilian physiologists and pharmacologists, who worked at the Instituto de Biologia de São Paulo, São Paulo, headed by Maurício Rocha e Silva. Together with colleagues Wilson Teixeira Beraldo and Gastão Rosenfeld, he discovered in 1948 whose strong hypotensive effects in animal models. Bradykinin was discovered ( Brazilian fer de lance snake ) in the blood plasma of animals after the addition of Bothrops jararaca Venom of which was provided by Rosenfeld from the Butantan Institute. This discovery was part of a continuing study on circulatory shock and proteolytic enzymes associated with the toxicology of snake bites, which was started by Rocha e Silva in 1939. Bradykinin should prove to be a new car pharmacological principle, ie as a substance that is released into the body over a metabolic modification of precursor substances that are pharmacologically active. After BJ Hagwood, Rocha e Silva's biographer, " the discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena, including venoms and toxins caused by circulatory shock. "

The practical significance of the discovery of bradykinin was apparently discovered when one of his employees at the Faculty of Medicine of Ribeirão Preto at the University of São Paulo, Sérgio Henrique Ferreira, a bradykinin - potentiating factor ( BPF) in the venom of Bothrops, both the duration and the extent of the effects of bradykinin on vasodilation and subsequent decrease in blood pressure significantly enhanced. Based on this finding, developed by researchers at BMS the first of a new generation of highly effective antihypertensive drugs, called ACE inhibitors such as captopril.

Credentials

  • Peptide hormone
Human Genome Organisation Smooth muscle tissue Arginine Proline Angiotensin-converting enzyme Renin–angiotensin system Bristol-Myers Squibb
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