Effects of Mg and Mn ions on the inhibitory action of cyclic nucleotides in the longitudinal myometrium of rat.

Contractile response, membrane activity, and fluorescence signal from mag-fura-2 were measured on the longitudinal myometrium taken from estrogen-treated rat, and the influence of Mg and Mn ions on the inhibitory effects caused by db cAMP, 8-bromo cGMP, and db cGMP was investigated. Taking the Kd value of mag-fura-2 with Mg to be 2.0 mM, the intracellular Mg concentration was estimated to be 380 microM in the tissue incubated with Mg-free Krebs solution and 420 microM in the tissue exposed to Ca-free 40 mM K solution containing 15 mM Mg for 5 min, respectively. The phasic contractions generated by electrical stimulation in Mg-free Krebs solution were more strongly depressed by 30 microM db cAMP, 10 microM 8-bromo cGMP, and 1 mM db cGMP after the Mg loading treatment. The muscle was exposed to Ca-free 40 mM K solution containing 0.6 mM Mn for 10 min, and it was assumed that the muscle was loaded with Mn ions. After the Mn loading treatment, the contractile depression caused by 8-bromo cGMP and db cGMP was enhanced, whereas that by db cAMP was attenuated. These results were discussed in relation to the influence of intracellular load with Mg or Mn on the inhibitory actions caused by isoprenaline, forskolin, and relaxin.