Molecular Classification
G protein-coupled receptor (GPCR), Receptor
Other Names
Bradykinin B2 receptor, BDKRB2 (gene name), BK-2 receptor, B₂R
Disease Roles
Inflammation and inflammatory diseases (e.g., asthma, rhinitis, arthritis, colitis)Pain disorders and nociceptionCardiovascular disease (hypertension, cardiac hypertrophy, myocardial infarction)

Bradykinin receptor B2 Overview

The **bradykinin receptor B₂**, encoded by the *BDKRB2* gene in humans,[1] is a **G protein-coupled transmembrane receptor that mediates most physiological responses to bradykinin**, a nine-amino-acid peptide hormone. The primary functions triggered by its activation include **vasodilation**, increased vascular permeability (**edema formation**), smooth muscle contraction/spasm, pain signaling through nociceptor stimulation,[3] as well as modulation of inflammatory responses via release of nitric oxide and prostaglandins.[1] The **receptor is constitutively expressed across many tissues**, unlike its inducible counterpart—the bradykinin B₁ receptor. Upon ligand binding (bradykinin or kallidin), conformational changes activate associated G proteins (**mainly Gq/Gi**) which then trigger downstream effectors such as phospholipase C. This leads to an increase in intracellular calcium concentration and subsequent cellular responses including further mediator release. The **receptor also forms complexes with angiotensin-converting enzyme**, linking it functionally with both renin–angiotensin system regulation and kinin–kallikrein system activity.[1] Clinically relevant drugs include selective antagonists like icatibant used for acute treatment of hereditary angioedema attacks due to their ability to block excessive vascular leakage mediated by this pathway.[10] Research continues into both agonist-based therapies for cardiovascular protection and antagonist-based therapies for various inflammatory disorders.

Mechanism of Action

Drugs targeting this molecule act by: - Antagonists block bradykinin binding to the B₂ receptor, inhibiting downstream pro-inflammatory and vasodilatory effects—used therapeutically in conditions like hereditary angioedema.[10] - Agonists stimulate the same pathways as endogenous bradykinin—potentially useful for cardiovascular protection via vasodilation or organ-protective effects.[2] The main intracellular mechanisms involve activation of Gq proteins leading to phospholipase C activation, increased intracellular calcium levels, nitric oxide release, prostaglandins production, and MAPK pathway stimulation.[1]

Biological Functions

Signal transduction
Vasodilation
Edema formation
Smooth muscle contraction/spasm
Nociceptor stimulation/pain signaling
Activation of mitogen‐activated protein kinase pathways

Disease Associations

Inflammation and inflammatory diseases (e.g., asthma, rhinitis, arthritis, colitis)
Pain disorders and nociception
Cardiovascular disease (hypertension, cardiac hypertrophy, myocardial infarction)
Edema-related conditions including hereditary angioedema
Neuropathy and neurodegenerative diseases such as Alzheimer’s disease
Cancer (lung cancer mentioned in context of potential roles)

Safety Considerations

  • Risk of excessive vasodilation leading to hypotension
  • Potential exacerbation of edema if not properly targeted
  • Pro-inflammatory actions may worsen some conditions if agonized rather than blocked
  • Therapeutic challenge lies in balancing beneficial cardiovascular/organ-protective effects with risk for inflammation/edema.

Interacting Drugs

Icatibant (“Hoe 140”)
FR173657
Other nonpeptide antagonists have been developed for research and clinical use.
Bradykinin peptide itself
Kallidin peptide

Associated Biomarkers

Biomarker
No widely established biomarkers specific for patient selection or efficacy monitoring are cited in these sources. However: - Polymorphisms in the BDKRB2 gene may modulate blood pressure response and microvascular function,[5] suggesting possible future biomarker utility.