Kinins are involved in the development of allergic nasal hyperresponsiveness in guinea pigs.
We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D4 was developed by a bradykinin B2 receptor agonist, bradykinin, but not by a bradykinin B1 receptor agonist, des-Arg10-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B2 but also B1 receptors.
Sugahara
Shingo
S
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Nabe
Takeshi
T
Mizutani
Nobuaki
N
Takenaka
Hiroshi
H
Kohno
Shigekatsu
S
D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007609:Kallidin / Q000031:analogs & derivatives* / Q000502:physiology; D007705:Kinins / Q000276:immunology* / Q000502:physiology; D017998:Leukotriene D4 / Q000276:immunology; D008297:Male; D017817:Nasal Lavage Fluid / Q000737:chemistry; D011058:Pollen / Q000276:immunology; D043783:Receptor, Bradykinin B1 / Q000819:agonists; D043782:Receptor, Bradykinin B2 / Q000819:agonists; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D000485:Allergens; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D007705:Kinins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D007609:Kallidin; C051090:bradykinin, Leu(8)-des-Arg(9)-; C052787:kallidin, des-Arg(10)-; D017998:Leukotriene D4; C065679:icatibant; D001920:Bradykinin