title: Effects of JTE-522, a specific inhibitor of cyclooxygenase-2, on the recurrence of allergic inflammation in rats.
abstract: JTE-522, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide , is a selective inhibitor of cyclooxygenase-2 at the enzyme level (IC50 is 6.4 x 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 E2 production and weakly inhibited cyclooxygenase-1-dependent prostaglandin E2 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 E2 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.
authors.affiliation: Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Migagi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Niki
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Yamaki
authors.forename: S
authors.initials: S
authors.lastname: Mue
authors.forename: K
authors.initials: K
authors.lastname: Ohuchi
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D006967:Hypersensitivity / Q000188:drug therapy*; D007527:Isoenzymes / Q000187:drug effects* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010080:Oxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D010544:Peroxidases / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000096926:Benzenesulfonamides
chemical_list: D001557:Benzenesulfonates; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007527:Isoenzymes; D010080:Oxazoles; D010544:Peroxidases; D011451:Prostaglandin-Endoperoxide Synthases; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides