Role of thromboxane A2 and platelet-activating factor in allergic bronchoconstriction in guinea pig airway in vivo.
Membrane-derived lipid mediators have been considered to play a major role in pathogenesis of bronchial asthma. However, the importance of and the interactions among each mediator are still unclear. We examined the role of thromboxane A2 (TXA2) and platelet-activating factor (PAF) in immediate asthmatic response (IAR) and interactions between these lipid mediators in guinea pig airway in vivo using a specific TXA2 antagonist S-1452 and a specific PAF antagonist Y-24180. We confirmed the activity of each antagonist, as S-1452 and Y-24180 significantly and dose-dependently inhibited bronchoconstriction induced by respective agonist inhalation. S-1452 inhibited IAR but Y-24180 did not, indicating that TXA2 plays a major role in IAR but PAF does not. S-1452 significantly inhibited PAF-induced bronchoconstriction but Y-24180 did not inhibit synthesized TXA2 (STA2)-induced bronchoconstriction, showing that the bronchoconstrictive effect of PAF is at least in part dependent on secondarily released TXA2, but TXA2 does not induce PAF production.
Saito
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Fujimura
M
M
Ogawa
H
H
Matsuda
T
T
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000633:toxicity; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000633:toxicity; D014230:Triazoles / Q000494:pharmacology
D000941:Antigens; D001381:Azepines; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010972:Platelet Activating Factor; D011982:Receptors, Prostaglandin; D014230:Triazoles; C056566:S 145; 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; D013928:Thromboxane A2; C037866:STA 2