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.