Influence of Mn ion the action of dibutyryl cyclic AMP and forskolin on contraction, membrane response, and cyclic AMP-dependent protein kinase activity in rat myometrium

Contractile response, membrane activity, and protein kinase A (PKA) activity were measured on the longitudinal muscle taken from the estrogen-treated rat uterus, and the influence of Mn ion on the inhibitory effects caused by db cAMP and forskolin was investigated. Phasic contractions generated in the muscle taken from the middle portion of uterus were depressed to 48 and 83% by 30 microM db cAMP and 0.1 microM forskolin in Mg-free Krebs solution, respectively; phasic contractions were more strongly depressed by the agents in the solution containing 0.2 mM Mn. Action potentials consisted of spike and plateau components, and the duration of the plateau potential was reduced by the application of the agents; membrane activity was more strongly depressed in the presence of 0.2 mM Mn. The contractile depression caused by db cAMP was reduced and by forskolin was enhanced by pretreatment of the tissue with 0.6 mM Mn for 30 min. The PKA activity was increased by 39 and 6% of the control, when 30 microM db cAMP and 0.1 microM forskolin were applied, respectively; the PKA activity in response to db cAMP and forskolin was reduced and enhanced, respectively, when the tissues were pretreated with 0.6 mM Mn. It was proposed that Mn ions permeated into cell interior when the muscle was exposed to 0.6 mM Mn, so that the effects of the agents were differently affected. It was also shown that plateau potential dominated in the muscle taken from the ovarian portion, and the contractile inhibition caused by the agents was far weaker.