title: Role of cyclooxygenase-2 for fluid secretion by the inflamed gallbladder mucosa.
abstract: Inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by activation of cyclooxygenase, which leads to an increase in prostaglandin formation. Cyclooxygenase exists as a constitutive (cyclooxygenase-l) and an inducible (cyclooxygenase-2) isoform. The aim of this study was to demonstrate the role of cyclooxygenase-2 in inflammatory fluid secretion of the feline gallbladder. Experiments were performed 10 weeks after a surgical procedure in which chronic cholecystitis was induced in cats by ligation of the cystic duct and implantation of a gallstone in the gallbladder. Gallbladder fluid transport was continuously monitored via a perfusion system. In inflammed gallbladders the continuous fluid secretion was reversed to absorption by intravenous injection of the selective cyclooxygenase-2 blocker, NS 398 (P <0.001). Increased levels of the inducible cyclooxygenase-2 were shown by immunoblotting in inflamed gallbladders. Selective pharmacologic blockage of cyclooxygenase-2 reduced the prostaglandin E2 release to the inflamed gallbladder lumen (P <0.01). These data suggest that cyclooxygenase-2 is involved in the inflammatory response during chronic cholecystitis. Selective cyclooxygenase-2 blockers may offer an alternative to traditional nonsterodial anti-inflammatory drugs with fewer side effects in patients with cholecystitis who are awaiting operation.
authors.affiliation: Institute for Surgical Sciences, Sahlgrenska University Hospital, G oteborg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Nilsson
authors.forename: D
authors.initials: D
authors.lastname: Delbro
authors.forename: L
authors.initials: L
authors.lastname: Hedin
authors.forename: S
authors.initials: S
authors.lastname: Friman
authors.forename: S
authors.initials: S
authors.lastname: Andius
authors.forename: J
authors.initials: J
authors.lastname: Svanvik
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D002415:Cats; D002764:Cholecystitis / Q000188:drug therapy / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005704:Gallbladder / Q000378:metabolism* / Q000473:pathology; D015151:Immunoblotting; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010544:Peroxidases / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin