The effect of metyrapone on uterine prostaglandin output and smooth muscle activity

Metyrapone, at low doses (0.5-1.0 mM), stimulated the output of both PGE and PGF from the isolated uterus of the pregnant rat determined following extraction of bath fluid, chromatographic separation and bioassay of the prostaglandin. At higher doses (2-4 mM), metyrapone inhibited PGF output, but had no effect on PGE output. Uterine activity was rapidly inhibited by metyrapone in a dose-related manner. This inhibition was not related to PG output as, at 1 mM metyrapone, activity was inhibited and PG output stimulated. Both metyrapone and papaverine produced dose-dependent inhibition of the activity of the isolated rabbit ileum, papaverine being 10 times more potent than metyrapone. Propranolol antagonised the response of the ileum to isoprenaline, but had no effect on the response to metyrapone. These observations confirm earlier data, suggsting that metyrapone exerts a differential effect on uterine PGE and PGF production and indicate that metyrapone has a direct inhibitory effect on smooth muscle activity.