Effect of a selective prostaglandin H synthase-2 inhibitor (NS-398) on prostaglandin production by the guinea-pig uterus.
Using guinea-pig uterine tissues, indomethacin (a non-selective inhibitor of prostaglandin H synthase) inhibited prostaglandin (PG) synthesis by homogenates of the endometrium, by cultured endometrium and myometrium, and by cultured epithelial glandular cells and stromal cells derived from the endometrium. NS-398, a selective inhibitor of prostaglandin H synthase-2 (PGHS-2), also inhibited PG synthesis by endometrial homogenates, by cultured endometrium and myometrium, and by cultured epithelial glandular cells and stromal cells. Indomethacin and NS-398 inhibited PG production to similar extents, except for 6-keto-PGF1 alpha production by the myometrium where indomethacin was more effective. In particular, indomethacin and NS-398 produced over 90% inhibition of PGF2 alpha output from the epithelial glandular cells, the main source of PGF2 alpha in the endometrium. These functional studies indicate that prostaglandin H synthase-2 is the predominant PG-forming enzyme in the guinea-pig uterus.
Naderali
E K
EK
Department of Pharmacology, University of Edinburgh Medical School, UK.
Poyser
N L
NL
D000818:Animals; D002478:Cells, Cultured; D046508:Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology*; D044262:Prostaglandin H2; D011453:Prostaglandins / Q000096:biosynthesis; D011463:Prostaglandins H; D011863:Radioimmunoassay; D013449:Sulfonamides / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011453:Prostaglandins; D011463:Prostaglandins H; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D044262:Prostaglandin H2; D007213:Indomethacin