JTE-522 selectively inhibits cyclooxygenase-2-derived prostaglandin production in inflammatory tissues.
OBJECTIVE
To investigate the effect of JTE-522, a selective cyclooxygenase (COX)-2 inhibitor, on prostaglandin (PG) production and COX expression in rats.


METHODS
Male rats (4-8 weeks old) were used for in vivo experiments, while for in vitro assay, rat peritoneal macrophages were used.


METHODS
JTE-522 (1-100 mg/kg) and indomethacin (0.03-10 mg/kg) were administered orally. JTE-522 and reference compounds (0.01-10 microM) were subjected to COX expression.


RESULTS
JTE-522 inhibited the development of carrageenin-induced paw edema and PGE2 production in inflammatory paws at a dose of 10 mg/kg. On the other hand, JTE-522 (1-100 mg/kg) did not affect A23187-stimulated thromboxane B2 release from whole blood or the PGE2 level in gastric mucosa. JTE-522 did not suppress lipopolysaccharide-induced COX-2 expression in peritoneal macrophages.


CONCLUSIONS
These results indicate that JTE-522 selectively inhibits PG production mediated by COX-2 in inflammatory tissues. JTE-522 may thus represent a novel type of anti-inflammatory drug without adverse effects on the gastro-intestinal tract.
Wakitani
K
K
Central Pharmaceutical Research Institute, Japan Tobacco, Inc., Takatsuki, Osaka, Japan. korekiyo.wakitani@ims.jti.co.jp
Tazaki
H
H
Matsushita
M
M
Iwamura
H
H
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D005528:Foot; D005753:Gastric Mucosa / Q000737:chemistry; D007249:Inflammation / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000097:blood; D000096926:Benzenesulfonamides
D001557:Benzenesulfonates; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007527:Isoenzymes; D010080:Oxazoles; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D013929:Thromboxane B2; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides