Effective diminution of amniotic prostaglandin production by selective inhibitors of cyclooxygenase type 2

Am J Obstet Gynecol. 2000 Feb;182(2):370-6. doi: 10.1016/s0002-9378(00)70226-2.

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.

Study design: 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.

Conclusion: Selective inhibitors of cyclooxygenase 2 are effective in diminishing prostaglandin production in vitro and may be useful in prevention of preterm deliveries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion / drug effects
  • Amnion / enzymology
  • Amnion / metabolism*
  • Blotting, Western
  • Chorion / drug effects
  • Chorion / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Decidua / drug effects
  • Decidua / metabolism
  • Dinoprostone / analysis
  • Dinoprostone / biosynthesis*
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoenzyme Techniques
  • Indomethacin / pharmacology
  • Indomethacin / therapeutic use
  • Isoenzymes / analysis
  • Isoenzymes / biosynthesis
  • Labor, Obstetric / drug effects*
  • Labor, Obstetric / metabolism
  • Myometrium / drug effects
  • Myometrium / metabolism
  • Nitrobenzenes / pharmacology
  • Nitrobenzenes / therapeutic use
  • Pregnancy
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Tocolytic Agents / pharmacology
  • Tocolytic Agents / therapeutic use

Substances

  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Nitrobenzenes
  • Pyrazoles
  • SC 560
  • Sulfonamides
  • Tocolytic Agents
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone
  • Indomethacin