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 PGD(2), PGE(2), PGF(2 alpha), 6-keto-PGE(1), and 6-keto-PGF(1 alpha) were constructed in the presence of indomethacin. Neither indomethacin nor tiaprofen in concentrations up to 100 mu mol/L had any effect upon spontaneous activity. Contractions were induced by the prostanoids with the following mean EC(50) values: PGE(2), 13 nM; PGF(2 alpha), 250 nM; PGD(2), 790 nM; both 6-keto-PGF(1 alpha) and 6-keto-PGE(1) were without effect in concentrations up to 30 mu mol/L. In some tissues PGE(2) 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.