Calcium-agonistic action of Mn2+ in the parathyroid cell

The effects of 3.0 mM Mn2+ on parathyroid hormone (PTH) release, 45Ca fluxes and the cytoplasmic Ca2+ concentration (Ca2+i) were studied in vitro with use of parathyroid glands from rats and cattle. Mn2+ inhibited PTH release by about 70 and 60% at Ca2+ concentrations of less than 10 nM or 0.5 mM, respectively, and like the inhibitory effect of Ca2+, that of Mn2+ was rapid and reversible. Mn2+-induced inhibition of the PTH release was associated with reduction of 45Ca uptake by about 50% and a marked but temporary increase in 45Ca efflux. Mn2+ induced a rapid transient increase in Ca2+i provided that the intracellular release of Ca2+ had not already been triggered by previous exposure to 3.0 mM Ca2+. This initial action was apparently followed by influx of Mn2+, since pronounced quenching of the fluorescence from the Ca2+ indicator fura-2 was observed. The results indicate that Mn2+ behaves in several respects like a calcium analogue in parathyroid cells and may inhibit PTH release by interfering directly with the secretory machinery.