Effects of some naturally occurring prostanoids and some cyclooxygenase inhibitors on the contractility of the human lower uterine segment in vitro

The contractility of strips of human lower segment myometrium obtained from elective cesarean section performed at term of pregnancy was studied in vitro. The effects of indomethacin and tiaprofen upon spontaneous contractile activity were examined. Concentration-effect curves for PGD2, PGE2, PGF2 alpha, 6-keto-PGE1, and 6-keto-PGF1 alpha were constructed in the presence of indomethacin. Neither indomethacin nor tiaprofen in concentrations up to 100 mumol/L had any effect upon spontaneous activity. Contractions were induced by the prostanoids with the following mean EC50 values: PGE2, 13 nM; PGF2 alpha, 250 nM; PGD2, 790 nM; both 6-keto-PGF1 alpha and 6-keto-PGE1 were without effect in concentrations up to 30 mumol/L. In some tissues PGE2 inhibited spontaneous activity with a mean IC50 of 100 nM. No other prostanoid tested caused inhibition under any circumstance. The marked potency differences between the natural prostanoids is an important parameter to consider when assessing their relative contributions to the process of parturition and the design of new therapeutic agents for the management of preterm labour.