Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.
1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen.
Ishida
K
K
UBC Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, B.C., Canada.
Thomson
R J
RJ
Schellenberg
R R
RR
D058927:5-Lipoxygenase-Activating Proteins; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000139:chemically induced / Q000473:pathology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology; D002722:Chlorobenzenes
D058927:5-Lipoxygenase-Activating Proteins; D000941:Antigens; D002352:Carrier Proteins; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; D010047:Ovalbumin; D013189:SRS-A; C060893:MK-886; D002722:Chlorobenzenes