Implication of the bradykinin receptors in antigen-induced pulmonary inflammation in mice

Br J Pharmacol. 2003 Apr;138(8):1589-97. doi: 10.1038/sj.bjp.0705207.


1. The involvement of bradykinin (BK) receptors in the allergic inflammation associated with airway hyper-reactivity (AHR) was evaluated by means of the selective bradykinin B(1) receptor (BKB(1)-R) antagonists R-715 (Ac-Lys-[D-betaNal(7), Ile(8)]desArg(9)-BK) and R-954 (Ac-Orn[Oic(2), alpha-MePhe(5), D-betaNal(7), Ile(8)]desArg(9)-BK) or the selective bradykinin B(2) receptor (BKB(2)-R) antagonist HOE-140 (D-Arg(0)-Hyp(3)-Thi(5)-D-Tic(7)-Oic(8)-BK). Cellular migration and AHR were examined 24 h after the second ovalbumin (OA) challenge. 2. R-715 (10-500 microg kg(-1)) and R-954 (1-100 microg kg(-1)) injected intravenously (i.v.), 5 min prior to aerosol OA challenges, decreased by approximately 50% the induced lung eosinophilia in OA-sensitized mice but did not reduce AHR. 3. HOE-140 (1 microg kg(-1)) administered in the same manner, decreased mononuclear cell and eosinophil infiltration in the bronchoalveolar lavage fluid (BALF) of OA-sensitized mice. Moreover, treatment of OA-sensitized mice with HOE-140 (100 microg kg(-1)) completely abolished the AHR to carbachol. 4. The BKB(1)-R agonist desArg(9)-BK (DBK; 10-1000 microg kg(-1)) administered intratrachealy to normal mice had no effect on the basal cell counts recovered in BALF nor on the plasma extravasation, while the BKB(2)-R selective agonist BK (20 microg kg(-1)) stimulated mononuclear cell migration, neutrophilia and plasma extravasation in normal mouse lungs. Such effects were inhibited by HOE-140 (10 microg kg(-1)). 5. Our results suggest that the airway inflammatory response induced by antigen challenge in mice is mediated by stimulation of both BKB(1)-R and BKB(2)-R.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / toxicity*
  • Bradykinin Receptor Antagonists
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / metabolism
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Receptors, Bradykinin / agonists
  • Receptors, Bradykinin / physiology*


  • Antigens
  • Bradykinin Receptor Antagonists
  • Receptors, Bradykinin