Bradykinin: A Mediator of Inflammation and Vascular Tone

Chemical Identity

Bradykinin is a linear nonapeptide of the kinin family, generated from high-molecular-weight kininogen (HMWK) by the serine protease kallikrein. It functions as a potent autocrine and paracrine mediator of vascular and inflammatory responses.

Property	Value
Chemical Formula	C₅₀H₇₃N₁₅O₁₁
Molecular Weight	1060.22 g/mol
CAS Number	5884-07-5
Isoelectric Point (pI)	11.8
Amino Acid Count	9
Disulfide Bridge	None (linear)

Primary Structure

Bradykinin has a well-defined linear sequence:

Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg

Notable structural features include:

• Proline residues at positions 2, 3, and 7, which induce kinks in the peptide backbone and constrain conformation
• C-terminal arginine essential for receptor activation
• N-terminal arginine contributing to overall basicity

Receptor Interactions

Bradykinin signals through two G-protein coupled receptors with distinct pharmacological profiles:

Receptor	G-Protein	Primary Coupling	Expression
B2	Gq/Gi	Constitutive	Ubiquitous, constitutive
B1	Gq/Gi	Inducible	Upregulated in inflammation

• B2 Receptor: Mediates acute responses; constitutively expressed; high affinity for native bradykinin
• B1 Receptor: Induced by cytokines (TNF-α, IL-1β); mediates sustained inflammatory responses; preferentially binds des-Arg⁹-bradykinin

Biological Functions

Bradykinin plays a central role in several pathophysiological processes:

1. Vasodilation: Activates endothelial B2 receptors → eNOS activation → nitric oxide (NO) and prostacyclin (PGI₂) release → smooth muscle relaxation.
2. Increased Vascular Permeability: Promotes plasma extravasation and edema formation via gap junction opening in endothelial cells.
3. Pain Signaling: Directly sensitizes nociceptors via B2 receptors and activates TRPV1 channels, producing acute hyperalgesia.
4. Inflammation: Amplifies the inflammatory cascade by stimulating cytokine release and immune cell recruitment.

Clinical Significance

Bradykinin is implicated in the pathophysiology of hereditary angioedema (HAE), where uncontrolled kinin generation leads to recurrent episodes of subcutaneous and submucosal swelling. ACE inhibitors potentiate bradykinin levels by inhibiting its enzymatic degradation, which contributes to both their antihypertensive effect and the side effect of dry cough or angioedema.

References

• Bhoola, K. D., et al. (2024). Kinins and kinin receptors in inflammation. Pharmacology & Therapeutics, 245, 108445.
• Campbell, D. J. (2003). The renin-angiotensin and the kallikrein-kinin systems. International Journal of Biochemistry & Cell Biology, 35, 784–791.