High extracellular Ca 2+ and Mg 2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells

Abstract

We examined the effects of the divalent cations Ca 2+ and Mg 2+ on inositol phosphate accumulation in bovine parathyroid cells prelabelled with [ 3H]inositol to determine whether the high extracellular Ca 2+ and Mg 2+-evoked transients in cytosolic Ca 2+ in these cells might result from increases in cellular IP 3 levels. In the presence of Li +, both Ca 2+ and Mg 2+ produced rapid, 2–6-fold increases in IP 3 and IP 2 and a linear increase in IP of 6–8-fold at 30 min. Smaller (1.5–2-fold) increases in IP 2 and IP 3 were evident within 7.5–15 s upon exposure to high (3mM) Ca 2+ in the absence of Li +. The relative potencies of Ca 2+ and Mg + (Ca 2+ 3-fold more potent than Mg 2+) in elevating inositol phosphates were similar to those for their effects in inhibiting PTH release. Fluoride (5 and 10 mM) also produced similar increases in inositol phosphate accumulation, presumably through activation of phospholipase C by a guanine nucleotide (G) protein-dependent process. Thus, high extracellular Ca 2+ and Mg 2+-induced spikes in cytosolic Ca 2+ in bovine parathyroid cells may be mediated by increases in IP 3, perhaps through a receptor-mediated process linked to phospholipase C by a G-protein.