Effect of anti-inflammatory agent etodolac on antigen-induced contractions of the trachea and lung parenchyma of guinea pigs.
Etodolac, which inhibits the activity of cyclooxygenase, did not affect antigen-induced contractions of the trachea and lung parenchyma of guinea pigs. Indomethacin tended to enhance antigen-induced contractions of the trachea and significantly enhanced contractions of the lung parenchyma. The inhibitory activity of AA-861, a 5-lipoxygenase inhibitor, in antigen-induced contractions of the trachea and lung parenchyma was more potent than that of ozagrel, a thromboxane A2 (TXA2) inhibitor. Thus, lipoxygenase products played a more important role than TXA2 in antigen-induced contractions of the trachea and lung parenchyma. These results suggest that the enhancement of antigen-induced contractions by indomethacin might be due to an increase in anaphylactic release of lipoxygenase products through the inhibition of cyclooxygenase. Since etodolac did not enhance antigen-induced contractions, we attempted to determine whether or not etodolac inhibits 5-lipoxygenase. Etodolac was found to have no effect on 5-lipoxygenase activity. Therefore, the low adverse effect of etodolac on antigen-induced contractions of the airway may be due to its weak inhibition of cyclooxygenase in the airway. These results suggest that etodolac would have only a very slight, if any, adverse effect on the airway in patients with asthma.
Inoue
K
K
Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
Hamada
K
K
Ueda
F
F
Shibata
Y
Y
Kimura
K
K
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016227:Benzoquinones / Q000494:pharmacology; D004195:Disease Models, Animal; D017308:Etodolac / Q000494:pharmacology*; D006168:Guinea Pigs; D007116:Immunization, Passive; D007213:Indomethacin / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology* / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008689:Methacrylates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000276:immunology* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects*
D016227:Benzoquinones; D007519:Isoantigens; D016859:Lipoxygenase Inhibitors; D008689:Methacrylates; D012710:Serum Albumin, Bovine; D017308:Etodolac; D013928:Thromboxane A2; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C034364:ozagrel; D007213:Indomethacin