title: Effective diminution of amniotic prostaglandin production by selective inhibitors of cyclooxygenase type 2.
abstract: OBJECTIVE
  Cyclooxygenase inhibitors are effective tocolytic agents, but significant adverse effects limit their use. We hypothesized that selective inhibitors of the isozyme cyclooxygenase 2 would effectively diminish labor-associated prostaglandin production.
  
  
  METHODS
  We analyzed cyclooxygenase type 1 and 2 expression in amnion, chorion, decidua, and myometrium from laboring or nonlaboring women and tested the efficacy of selective cyclooxygenase 2 inhibition in diminishing prostaglandin production.
  
  
  RESULTS
  The expression of cyclooxygenase 2 in amnion from women in labor, either preterm or at term, was significantly higher than in amnion before labor. In contrast, cyclooxygenase 1 expression was unchanged by labor. The enhanced expression of amniotic cyclooxygenase 2 was associated with increased prostaglandin E(2) levels in laboring women. Amniotic prostaglandin E(2) production was effectively diminished by the selective cyclooxygenase 2 inhibitors SC-236 and NS-398 but not by the cyclooxygenase 1 inhibitor SC-560.
  
  
  CONCLUSIONS
  Selective inhibitors of cyclooxygenase 2 are effective in diminishing prostaglandin production in vitro and may be useful in prevention of preterm deliveries.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sadovsky
authors.forename: D M
authors.initials: DM
authors.lastname: Nelson
authors.forename: L J
authors.initials: LJ
authors.lastname: Muglia
authors.forename: G A
authors.initials: GA
authors.lastname: Gross
authors.forename: K C
authors.initials: KC
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Koki
authors.forename: J L
authors.initials: JL
authors.lastname: Masferrer
authors.forename: L M
authors.initials: LM
authors.lastname: Olson
mesh_terms: D000650:Amnion / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D002823:Chorion / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003656:Decidua / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D007743:Labor, Obstetric / Q000187:drug effects* / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D015149:Tocolytic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000096926:Benzenesulfonamides
chemical_list: D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin; D007527:Isoenzymes; D009578:Nitrobenzenes; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; D015149:Tocolytic Agents; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C115461:SC 560; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide