Bradykinins (BKs) belong to a family of short, structurally similar peptides that are important metabolites of the kallikrein-kinin system. They are vasoactive nonapeptides formed by action of proteases on the high-molecular-weight kininogen during the contact phase of blood coagulation, resulting in endothelium-dependent vasodilatation and stimulation of tissue plasminogen activator release from human endothelial cells. Bradykinin is released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may act as a neurotransmitter. It directly activates afferent neurons via G protein-coupled bradykinin B2 receptors. Bradykinin inhibits a calcium-dependent potassium current responsible for an afterspike hyperpolarization in nodose ganglion. Bradykinin-induced Ca2+ increase in cells is mediated by the stimulation of kinin receptors of the B2 subtype. Bradykinin also contracts smooth muscles, and is a potent stimulator of nitric oxide formation by vascular endothelium. It also stimulates prostacyclin formation. Bradykinin is involved in edema resulting from trauma or injury and aid in dissolving blood clots. When it is secreted by eccrine sweat glands, it causes the surface of blood vessels to dilate and help radiate excessive heat from the body surface, making it an important peripheral thermoregulatory molecule.
Bradykinin production in the lung increases with many pulmonary diseases such as asthma, bronchitis, and pneumonia.
Ref: Carr, M. et al. J. Pharmacol. Exp. Ther. 304, 1275 (2003); Wennemuth, G. et al. Brit. J. Pharmacol. 138, 351 (2003); Witherow, F. et al. Arterioscler. Thromb. Vasc. Biol. 23, 1667 (2003); Soukhova, G. et al. J. Appl. Physiol. 95, 241 (2003); Wirth, KJ. et al. Am. Rev. Respir. Dis. 148, 702 (1993).