Mechanism of mifepristone-induced spasmolytic effect on isolated rat uterus

Mifepristone, a synthetic 19-norsteroid relaxed the KCl-induced tonic contr action in isolated rat uterus in a concentration-dependent way and CaCl2 (0 .1 to 10 mM) counteracted it. This effect was similar to other steroids alt hough the mechanisms involved are unclear. Before adding the contracturant, tissue was incubated with actinomycin D (10 mu M), cycloheximide (300 mu M ), TPCK (3 and 10 mu M), Rp-cAMPS (30 mu M), DDA (100 mu M) and H-7 (1 mu M ). None of these modified the relaxing effect of mifepristone. Incubation w ith drugs that interfere with cGMP such as a nucleotide analogue DDG (100 m u M), a soluble guanylyl cyclase inhibitor ODQ (1 mu M) and an inhibitor of protein kinase G 8pCPTcGMPS (1 mu M) significantly modified the effect of mifepristone, increasing its IC50.