Effect of magnesium on parathyroid cells: Evidence for two sensing receptors or two intracellular pathways?

It currently remains controversial as to the intracellular mechanisms coupled to the inhibition of parathyroid hormone (PTH) secretion that are modulated by extracellular divalent cations. To study mechanisms responsible for regulation of PTH release by cations, we investigated the effect of Mg2+ on cytosolic Ca2+ levels ([Ca2+](i)) and PTH secretion in single isolated bovine parathyroid cells. Addition of 9.0 mM Mg2+ evoked a spike of [Ca2+](i) in similar to 80% of cells in the presence of extracellular Ca2+. Mg2+ decreased steady-state [Ca2+](i), which represented inhibition of influx of extracellular Ca2+ in 13-78% of cells. The percentage of cells that had a decline in steady-state [Ca2+](i) after exposure to Mg2+ was dependent on the extracellular Ca2+ concentration. The effect of Mg2+ on intracellular Ca2+ response was dose dependent. Extracellular Mg2+ inhibited PTH secretion in cells that showed decline in steady-state [Ca2+](i), although cells that showed a spike after addition of Mg2+ secreted more PTH than cells that did not show a spike. The spike of [Ca2+](i) and decline in steady-state [Ca2+](i) that occur in response to extracellular Mg2+ may be caused independently by two distinct mechanisms that differentially regulate secretion of PTH.