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 inhibi tor of prostaglandin H synthase) inhibited prostaglandin (PG) synthesi s by homogenates of the endometrium, by cultured endometrium and myome trium and by cultured epithelial glandular cells and stromal cells der ived from the endometrium. NS-398, a selective inhibitor of prostaglan din H synthase-2 (PGHS-2), also inhibited PG synthesis by endometrial homogenates, by cultured endometrium and myometrium, and by cultured e pithelial glandular cells and stromal cells. Indomethacin and NS-398 i nhibited PG production to similar extents, except for 6-keto-PGF(1 alp ha) production by the myometrium where indomethacin was more effective . In particular, indomethacin and NS-398 produced over 90% inhibition of PGF(2 alpha) output from the epithelial glandular cells, the main s ource of PGF2 alpha in the endometrium. These functional studies indic ate that prostaglandin H synthase-2 is the predominant PC-forming enzy me in the guinea-pig uterus.