Bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is produced when the serine protease plasma kallikrein cleaves the precursor protein high-molecular-weight kininogen (HMWK). The resulting nonapeptide acts principally at two G-protein-coupled receptor subtypes: B1 and B2. The B2 receptor is constitutively expressed and mediates most acute physiological responses; the B1 receptor is largely inducible and is upregulated in the presence of tissue injury or inflammatory stimuli.
Physiologically, bradykinin promotes vasodilation through endothelial release of nitric oxide and prostacyclin, increases vascular permeability, and activates afferent nociceptive fibres. It is also a substrate for angiotensin-converting enzyme (ACE), which degrades it to inactive fragments , a process that becomes clinically relevant when ACE inhibitor drugs are present, since reduced bradykinin degradation is associated with the characteristic dry cough observed with that drug class.
Bradykinin has a very short plasma half-life, typically under 30 seconds, owing to rapid degradation by kininases including ACE and carboxypeptidase N. Because of this rapid inactivation, it acts principally in a local, paracrine fashion rather than as a circulating hormone. Research interest in the kallikrein–kinin system covers areas including cardiovascular regulation, oedema formation, and neurogenic inflammation; however, findings from in vitro and animal models do not automatically translate to human physiology, and the clinical significance of specific mechanistic findings continues to be evaluated.
Synthetic bradykinin analogues and receptor antagonists have been investigated as research tools and as candidate therapeutic agents. In Australia, any synthetic peptide analogue that has not received marketing approval from the Therapeutic Goods Administration (TGA) and is not listed on the Australian Register of Therapeutic Goods (ARTG) is an unapproved therapeutic good. Supplying such substances without the requisite TGA approval is illegal under the Therapeutic Goods Act 1989 (Cth). Researchers requiring bradykinin-related compounds for legitimate purposes must operate within applicable institutional, state, and Commonwealth regulatory frameworks.
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