title: Differing profiles of prostaglandin formation inhibition between selective prostaglandin H synthase-2 inhibitors and conventional NSAIDs in inflammatory and non-inflammatory sites of the rat.
abstract: The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.forename: M
authors.initials: M
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Hatanaka
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Ogino
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Ogino
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005750:Gastric Juice / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D012965:Sodium Chloride; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; D001241:Aspirin; C012655:nimesulide; D007213:Indomethacin