Kallidin
Also known as: Lysyl-bradykinin, Lys-bradykinin, Lys-BK, KD
Endogenous kinin peptide; member of the kallikrein-kinin system
What it is
Researchers studying inflammation, pain signalling, blood pressure regulation, and cardiovascular disease have long investigated kallidin. It is a naturally occurring peptide produced in the body from kininogen precursors, and it acts on the same receptors as the better-known bradykinin, making it a key player in the kallikrein-kinin system.
The scientific side
kallidin (lysyl-bradykinin, Lys-BK) is a ten-amino-acid endogenous kinin peptide generated from kininogen precursors through the enzymatic action of tissue kallikrein (KLK1), which cleaves both high- and low-molecular-weight kininogens to release kallidin. It is the decapeptide counterpart of the nonapeptide bradykinin, differing only by an additional N-terminal lysine residue. Both peptides are primary agonists of the bradykinin B2 receptor (B2R), a G protein-coupled receptor constitutively expressed in healthy tissues. Cryo-EM structures of human B2R-Gq complexes with kallidin resolved at 2.9 Å demonstrate that kallidin binds an S-shaped ligand-binding pocket in B2R, with aspartate and glutamate residues forming an anion trap and phenylalanine residues at the peptide tail inducing conformational changes in the W283 toggle switch and conserved PIF, DRY, and NPxxY motifs, ultimately driving Gq protein coupling and downstream signalling. B2R activation signals through Gαq to stimulate phospholipase Cβ, leading to phosphoinositide hydrolysis, intracellular calcium mobilisation, and through Gαi to inhibit adenylate cyclase and activate mitogen-activated protein kinase pathways. When carboxypeptidases (kininase I, comprising carboxypeptidase N and carboxypeptidase M) cleave the C-terminal arginine from kallidin, the metabolite des-Arg10-kallidin (DAKD) is generated. DAKD is the primary endogenous agonist of the bradykinin B1 receptor (B1R), which is expressed at very low levels under baseline conditions but is strongly induced by tissue injury and proinflammatory cytokines such as interleukin-1β. Circulating plasma kallidin levels in healthy individuals are in the very low picomolar range (below the levels of bradykinin), while levels in nasal epithelial lining fluid reach a median of approximately 80 pM as measured by validated LC-MS/MS methods. The dual-receptor system—B2R mediating acute vasodilatory and anti-inflammatory responses to kallidin, and B1R mediating sustained inflammatory responses to its metabolite DAKD—places kallidin at a central regulatory node in vascular tone, pain transmission, oedema formation, and immune cell recruitment.
Class: Endogenous kinin peptide; member of the kallikrein-kinin system
Administration & storage
- Administration
- Intravenous infusion (for human urinary kallidinogenase in clinical trials — slow drip over at least 50 minutes)
- Storage
- No specific storage instructions for synthetic kallidin peptide are reported in the reviewed abstracts. As a peptide, standard cold-chain storage (2–8°C for prepared solutions; frozen for lyophilised stock) would be expected based on general peptide handling principles, but this is not directly sourced from the fetched literature.
Legal & regulatory status
Kallidin itself is not an approved drug product. Human urinary kallidinogenase (an enzyme that generates kallidin) is approved in China but not by the US FDA. No FDA-approved therapeutic directly delivers kallidin. The…
Kallidin is not identified as a prohibited substance in the reviewed literature. No WADA classification is reported in the fetched abstracts.
No approved drug product delivering kallidin directly is identified in the reviewed literature. No Health Canada approval status is reported in the fetched abstracts.
What it's studied for
- Hypertension and blood pressure regulation Preclinical (animal models); indirect clinical evidence via ACE inhibitor pharmacology
- Acute ischemic stroke — cerebral perfusion enhancement Clinical (Phase 2/4 trials in China; not FDA-approved)
- Cardiovascular and renal protection in ischaemia and diabetes Preclinical and indirect clinical (ACE inhibitor evidence)
- Retinal neovascularisation and pathological angiogenesis Preclinical (animal models)
- Intestinal ion secretion and inflammation Preclinical (ex vivo porcine tissue)
- Hereditary angioedema — mechanistic role in swelling episodes Mechanistic/translational (human genetics and in vitro)
- Middle ear inflammation and otitis media Preclinical (primary cell cultures)
Safety signals
- Hypotension and vasodilation — acute B2R-mediated effect
- Angioedema — kinin-mediated swelling of skin and mucosal membranes
- Pro-inflammatory and pro-oedematous tissue effects via B2R activation
- Bronchoconstriction in asthmatic and atopic individuals
- Neurogenic intestinal secretion and potential diarrhoea
- Cardiac remodelling and fibrosis — B1R-mediated when kallidin is metabolised to des-Arg10-kallidin
- Retinal neovascularisation — pro-angiogenic and pro-inflammatory via B2R
All studies (4)
Frequently asked
What is the difference between kallidin and bradykinin?
Kallidin (lysyl-bradykinin) is a ten-amino-acid peptide, while bradykinin is a nine-amino-acid peptide. The only structural difference is an additional lysine at the N-terminus of kallidin. Both peptides are produced from kininogen precursors by kallikrein enzymes and both activate the bradykinin B2 receptor. Tissue kallikrein preferentially generates kallidin, while plasma kallikrein preferentially generates bradykinin. Cryo-EM structural studies confirm both bind the same S-shaped ligand pocket in B2R with similar activation mechanisms.
Is kallidin available as a therapeutic drug?
Based on the reviewed literature, kallidin itself is not approved as a therapeutic drug by the US FDA or other major regulators described in the abstracts. However, the enzyme that generates kallidin — tissue kallikrein (as human urinary kallidinogenase, HUK) — is approved in China for the subacute treatment of acute ischaemic stroke and has been studied in multiple clinical trials. There are no reports of direct administration of synthetic kallidin peptide to humans in the reviewed literature.
What receptors does kallidin act on?
Kallidin primarily activates the bradykinin B2 receptor (B2R), which is constitutively expressed in healthy tissues and mediates vasodilation, pain, and vascular permeability responses. When the enzyme kininase I (carboxypeptidase N or M) removes the C-terminal arginine from kallidin, it produces des-Arg10-kallidin, which is the primary agonist of the bradykinin B1 receptor (B1R). B1R is barely expressed in healthy tissue but is strongly induced by tissue injury and inflammation. BRET-based assays show that kallidin activates a distinct profile of G protein subtypes at B2R compared with bradykinin, indicating biased signalling between the two kinin peptides.
How is kallidin measured in blood or tissue?
Kallidin is measured in plasma and biological fluids using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) platforms. In healthy volunteers, plasma kallidin concentrations are in the very low picomolar range, below 4.2 pM for bradykinin, with kallidin at even lower levels. Nasal epithelial lining fluid contains substantially higher levels, with median kallidin at approximately 80 pM. Accurate measurement requires specialised protease-inhibitor-prespiked collection tubes because of kallidin's short half-life and susceptibility to ex vivo degradation.
Is kallidin involved in COVID-19?
The reviewed literature notes that SARS-CoV-2 binds ACE2 on cell surfaces, downregulating ACE2 and impairing the degradation of bradykinin and des-Arg9-bradykinin. Kininogens in plasma and tissue are the main sources of both bradykinin and kallidin, and the 'bradykinin storm' hypothesis proposes that dysregulation of the kinin system contributes to pulmonary oedema in severe COVID-19. LC-MS/MS assays have been developed to measure kallidin and related kinins in nasal lavage fluid specifically to investigate these proposed COVID-19 pathophysiological changes.