RELATIONSHIP BETWEEN MN-INDUCED CONTRACTILE INHIBITION AND CYCLIC-AMPCONTENT IN THE LONGITUDINAL MUSCLE OF ESTROGEN-TREATED RAT UTERUS

In longitudinal myometrial strips of estrogen-treated rats, nifedipine (0.03 mu M) induced the gradual inhibition of phasic contractions evo ked by repetitive electrical stimulations, with inhibition reaching a plateau level (43.4+/-2.6% of the control group, n=6) within 20 min. I n contrast, 0.5mM Mn induced a rapid and transient suppression of the phasic contractions (58.3+/-8.9% of the control group, n=10, at 4 min) followed by sustained inhibition of the contractions, the level of wh ich was slightly lower than that of the control group (84.2+/-5.0%, n= 10, at 20 min). The Mn also induced a rapid and transient increase in cellular cAMP level, which reached a peak (201.2+/-20.8% of the contro l group, n=5) at 2 min and decreased to the prestimulation level (=100 %) within 15min. Pretreatment with 1 mM isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, potentiated the effect of Mn on the cA MP level. The transient effects of Mn, but not of nifedipine, on the c ontractions and cAMP levels (and their potentiation by IBMX) do not su pport the simple action of Mn as a Ca antagonist, but are compatible w ith the intracellular dual action of Mn on adenylate cyclase.