Bradykinini

Bradykinini, typically referred to in English as bradykinin and related kinins, are short peptides that act as mediators in inflammation and vascular regulation. The most studied member is bradykinin, a nonapeptide that can stimulate receptor signaling to cause vasodilation, increased vascular permeability, and pain.

Biosynthesis and relations: They are generated in the plasma by the action of plasma kallikrein on high-molecular-weight kininogen (HMWK). The kallikrein-kinin system becomes activated in response to tissue injury or inflammatory signals. A related peptide, kallidin, can be formed when tissue kallikrein acts on low-molecular-weight kininogen.

Mechanism of action: Bradykinin signals mainly through the B2 receptor, a G-protein-coupled receptor, leading to vasodilation via nitric oxide and prostacyclin, as well as increased vascular permeability and pain. The B1 receptor is induced in chronic inflammation and recognizes des-Arg-bradykinin.

Metabolism and regulation: Bradykinin has a very short half-life due to rapid enzymatic breakdown by kininases such as angiotensin-converting enzyme (ACE) and aminopeptidases. Des-Arg-bradykinin is inactivated by carboxypeptidases; ACE inhibitors raise bradykinin levels.

Clinical significance: Dysregulation of bradykinin signaling is implicated in hereditary angioedema due to C1 esterase inhibitor deficiency, which leads to unchecked kallikrein activity and excess bradykinin. ACE inhibitors are associated with cough and angioedema through increased bradykinin. Therapeutically, bradykinin B2 receptor antagonists, such as icatibant, are used to treat acute angioedema attacks. Ongoing research explores bradykinin’s roles in pain, inflammatory diseases, and cardiovascular pathology.