Involvement of cyclooxygenase-2 in allergic nasal inflammation in rats.
This study was undertaken to investigate the involvement of cyclooxygenase-2 (COX-2) in allergic nasal inflammation in actively sensitized rats. An allergic rhinitis model was developed by the repeated topical application of antigen into the nasal cavities in the sensitized rats. The severity of allergic rhinitis was studied by measuring the nasal behavior, as well as electroencephalogram (EEG) activity by antigen challenge. The electrodes were implanted chronically into the bilateral olfactory bulb of the rats and the EEG was measured monopolarly with an electroencephalograph (EEG, Nohon Kohden, Japan). The intranasal application of antigen caused the increase of nasal allergic signs as well as an EEG spike in a dose-dependent fashion, and at a dose of 50 microg/site, it showed a significant effect. The responses induced by the antigen were evaluated with certain drugs, etodolac (a selective COX-2 inhibitor), indomethacin (a non-selective COX inhibitor), ramatroban (a thromboxane A2 receptor antagonist) and zafirlukast (a cys-leukotriene receptor antagonist). Etodolac showed the inhibition of nasal behavior and EEG spike in a dose-related fashion, and at doses of 3 and 10 mg/kg, it showed a significant effect. Moreover, ramatroban also caused the dose-related inhibition of nasal behavior and EEG spike induced by antigen. On the other hand, both indomethacin and zafirlukast had no effects on the responses induced by antigen, even at a higher dose. Therefore, it can be concluded that cyclooxygenase-2 actively participates in the allergic nasal inflammation in actively sensitized rats.
Rahman
Ashequr
A
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
Yatsuzuka
Rie
R
Jiang
Shuishi
S
Ueda
Yuhki
Y
Kamei
Chiaki
C
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000276:immunology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D017308:Etodolac / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007211:Indoles; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D009830:Olfactory Bulb / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D048448:Phenylcarbamates; D051381:Rats; D017208:Rats, Wistar; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D012220:Rhinitis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D012912:Sneezing / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology
D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013449:Sulfonamides; D014105:Tosyl Compounds; D017308:Etodolac; D010047:Ovalbumin; D051546:Cyclooxygenase 2; C063119:ramatroban; D007213:Indomethacin; C062735:zafirlukast