The uptake of manganese induced by agonists in the isolated vas deferens of the guinea pig.

The uptake of manganese (Mn) induced by 100 mM potassium (K), 10 microM norepinephrine (NE) or 10 microM acetylcholine (ACh) was measured by atomic absorption spectroscopy in isolated vas deferens of the guinea pig. The agonists at these concentrations caused the maximal contraction of the vas deferens. The contents of Mn were increased with the repetitive treatments of Mn with K and were not significantly decreased after 1 h washing. The uptake of Mn was also stimulated by NE and ACh. The stimulation of uptake of Mn by K was the most potent while that by ACh was the smallest. The uptake of Mn was enhanced by elimination of Ca from the medium, while inhibited by the higher concentration of external Ca and by 2.1 microM diltiazem. The time course of K-induced Mn uptake was biphasic: an initial faster phase and a following slower phase of accumulation. The extents of increments of the Mn contents were dependent on the order of the applications of K and Mn: the increments became smaller in the following order, 1) when Mn was applied prior to K, 2) Mn was applied simultaneously with K, 3) Mn was applied after K. These results suggested that superficially bound Mn penetrates into the smooth muscle cells of vas deferens during the stimulation by agonists through the voltage-dependent calcium-channel (VDC) and that intracellular Mn was hardly extruded. It was also suggested that the degree of activation of VDC, through which Mn can enter the cells, was in the following order, K greater than NE greater than ACh. These results were consistent with our previous report about the dual effects of Mn: the inhibition and potentiation of contractions. It was also suggested that Mn may be a useful tool as a Ca analogue because Mn can penetrate into cells through VDC and, once taken up into the cells, Mn is not readily extruded and remains in the cells even after extracellular Mn is washed away.