Abstract

In longitudinal myometrial strips of estrogen-treated rats, nifedipine (0.03 microM) induced the gradual inhibition of phasic contractions evoked by repetitive electrical stimulations, with inhibition reaching a plateau level (43.4 +/- 2.6% of the control group, n = 6) within 20 min. In contrast, 0.5 mM 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 which 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 control group, n = 5) at 2 min and decreased to the prestimulation level ( = 100%) within 15 min. Pretreatment with 1 nM isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, potentiated the effect of Mn on the cAMP level. The transient effects of Mn, but not of nifedipine, on the contractions and cAMP levels (and their potentiation by IBMX) do not support the simple action of Mn as a Ca antagonist, but are compatible with the intracellular dual action of Mn on adenylate cyclase.

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