Role of leukotrienes and platelet activating factor in allergic bronchoconstriction and their interactions in guinea pig airway in vivo.
Membrane-derived lipid mediators have been considered to play a major role in pathogenesis of bronchial asthma. Recently specific antagonists and synthetase inhibitors of some chemical mediators have been developed and many studies on their anti-asthmatic effects are ongoing. But the importance of and the interactions of each mediator are still unclear. We examined the role of leukotrienes (LTs) and platelet activating factor (PAF) in immediate asthmatic response (IAR) and interactions between these lipid mediators in guinea pig airways in vivo using a specific LTs antagonist AS-35 and a specific PAF antagonist Y-24180. We confirmed the activity of each antagonist, as AS-35 and Y-24180 inhibited bronchoconstriction induced by respective agonist inhalation. AS-35 inhibition IAR but Y-24180 did not, indicating that LTs play a major role in IAR but PAF does not. AS-35 did not influence PAF-induced bronchoconstriction and Y-24180 did not inhibit LTs-induced bronchoconstriction, showing that there is no interaction between LTs and PAF.
Saito
M
M
Third Department of Internal Medicine, Kanazawa-University School of Medicine, Japan.
Fujimura
M
M
Ogawa
H
H
Matsuda
T
T
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D006168:Guinea Pigs; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D001993:Bronchodilator Agents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011725:Pyridines; D011744:Pyrimidinones; D013777:Tetrazoles; D014230:Triazoles; C073308:AS 35; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine