High extracellular Ca2+ and Mg2+ stimulate accumulation of inositol phosphates in bovine parathyroid cells

Abstract

We examined the effects of the divalent cations Ca²⁺ and Mg²⁺ on inositol phosphate accumulation in bovine parathyroid cells prelabelled with [³H]inositol to determine whether the high extracellular Ca²⁺ and Mg²⁺-evoked transients in cytosolic Ca²⁺ in these cells might result from increases in cellular IP₃ levels. In the presence of Li⁺, both Ca²⁺ and Mg²⁺ produced rapid, 2–6-fold increases in IP₃ and IP₂ and a linear increase in IP of 6–8-fold at 30 min. Smaller (1.5–2-fold) increases in IP₂ and IP₃ were evident within 7.5–15 s upon exposure to high (3mM) Ca²⁺ in the absence of Li⁺. The relative potencies of Ca²⁺ and Mg⁺ (Ca²⁺ 3-fold more potent than Mg²⁺) 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 Ca²⁺ and Mg²⁺-induced spikes in cytosolic Ca²⁺ in bovine parathyroid cells may be mediated by increases in IP₃, perhaps through a receptor-mediated process linked to phospholipase C by a G-protein.