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 (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.
Institute of Pharmacology of Sherbrooke, School of Medicine, University of Sherbrooke, Sherbrooke, PQ, Canada J1H 5N4.
Jadranka
J
Eric
Bichoy H
BH
Gabra
Pierre
P
Sirois
D000818:Animals; D000941:Antigens / Q000633:toxicity*; D065168:Bradykinin Receptor Antagonists; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*
D000941:Antigens; D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin