Effective diminution of amniotic prostaglandin production by selective inhibitors of cyclooxygenase type 2.
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.
Sadovsky
Y
Y
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri, USA.
Nelson
D M
DM
Muglia
L J
LJ
Gross
G A
GA
Harris
K C
KC
Koki
A
A
Masferrer
J L
JL
Olson
L M
LM
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
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