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

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 (BKB1-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 (BKB2-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 mug kg(-1)) and R-954 (1-100 mug 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 mug 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 mug kg(-1)) completely abolished the AHR to carbachol. 4 The BKB1-R agonist desArg(9)-BK (DBK; 10-1000 mug 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 BKB2-R selective agonist BK (20 mug kg(-1)) stimulated mononuclear cell migration, neutrophilia and plasma extravasation in normal mouse lungs. Such effects were inhibited by HOE-140 (10 mug kg(-1)). 5 Our results suggest that the airway inflammatory response induced by antigen challenge in mice is mediated by stimulation of both BKB1-R and BKB2-R.