Modification of allergen-induced airway obstruction and airway hyperresponsiveness in an allergic rabbit model by the selective platelet-activating factor antagonist, BN 52021.
Allergen challenge of eight ragweed-immunized rabbits elicited a prolonged airway obstruction that was evident during the 6-hour study period. Airway responsiveness to histamine was enhanced 24 hours after allergen exposure (geometric mean of the 50% reduction in effective dose [ED50] of dynamic compliance [Cdyn] before challenge, 3.46 mg/ml, decreased to 0.52 mg/ml after challenge, p less than 0.01; pulmonary resistance ED50 geometric mean before challenge, 3.50 mg/ml, decreased to 0.65 mg/ml after challenge, p less than 0.05). In a random crossover study, the selective platelet-activating factor antagonist, BN 52021 (60 mg/kg, orally, 1 hour before allergen challenge), significantly reduced the allergen-induced airway obstruction (p less than 0.005). In addition, pretreatment with BN 52021 reduced the associated increased airway responsiveness induced by allergen exposure (prechallenge Cdyn ED50, 1.93; after challenge, 2.13 mg/ml; pulmonary resistance ED50, 1.91 mg/ml before challenge and 1.69 mg/ml after challenge). These present observations suggest a role for platelet-activating factor in the pathogenesis of allergen-induced airway obstruction and in the development of airway hyperresponsiveness in an allergic rabbit model.
Coyle
A J
AJ
Department of Pharmacology, Kings College, University of London, England.
Page
C P
CP
Atkinson
L
L
Sjoerdsma
K
K
Touvay
C
C
Metzger
W J
WJ
D000402:Airway Obstruction / Q000276:immunology*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced; D004224:Diterpenes; D046934:Ginkgolides; D006632:Histamine; D007783:Lactones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D010936:Plant Extracts; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology
D000485:Allergens; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D006632:Histamine; C045856:ginkgolide B