Effects of JTE-522, a specific inhibitor of cyclooxygenase-2, on the recurrence of allergic inflammation in rats

JTE-522, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, is a selective inhibitor of cyclooxygenase-2 at the enzyme level (IC 50 is 6.4×10 −7 M for sheep cyclooxygenase-2, but it does not inhibit sheep cyclooxygenase-1 at concentrations up to 10 −4 M). In rat peritoneal macrophages...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:European journal of pharmacology 1998-03, Vol.344 (2), p.261-267
Hauptverfasser: Niki, Hisae, Yamada, Masateru, Yamaki, Kouya, Mue, Suetsugu, Ohuchi, Kazuo
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:JTE-522, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide, is a selective inhibitor of cyclooxygenase-2 at the enzyme level (IC 50 is 6.4×10 −7 M for sheep cyclooxygenase-2, but it does not inhibit sheep cyclooxygenase-1 at concentrations up to 10 −4 M). In rat peritoneal macrophages in culture, it markedly inhibited cyclooxygenase-2-dependent prostaglandin E 2 production and weakly inhibited cyclooxygenase-1-dependent prostaglandin E 2 production, as did the selective cyclooxygenase-2 inhibitor NS-398 ([ N-2(cyclohexyloxy-4-nitrophenyl)]-methanesulfonamide). In addition, the anti-inflammatory activity of JTE-522 was evaluated, using a model of recurrent air pouch-type allergic inflammation in rats. JTE-522, injected into the pouch just after a second antigen challenge, suppressed the accumulation of pouch fluid, the infiltration of leukocytes and the prostaglandin E 2 content in the pouch fluid, as did NS-398 and indomethacin. These findings indicated that JTE-522 is a selective cyclooxygenase-2 inhibitor in cell culture systems and that the suppression by JTE-522 of the recurrence of allergic inflammation is due to the inhibition of cyclooxygenase-2.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(97)01591-4