The effects of high extracellular Ca2+ and Mg2+ concentrations on the levels of inositol 1,3,4,5-tetrakisphosphate in bovine parathyroid cells.

We examined the effects of calcium (Ca2+), magnesium (Mg2+), and fluoride ion (F-) on inositol phosphate accumulation in bovine parathyroid cells prelabeled with [3H] inositol to determine whether these agents might modulate cytosolic Ca2+ through accumulation of intracellular inositol 1,3,4,5-tetrakisphosphate (IP4), which has been postulated to be a mediator of the influx of extracellular Ca2+. Both Ca2+ and Mg2+ produced dose-dependent increases in IP4 in the presence of Li+, with maximal 19- and 4-fold increases with 5.0 mM Ca2+ and 20 mM Mg2+, respectively. A 50% rise in IP4 was evident within 1 min in response to 5.0 mM Ca2+. In the absence of Li+, a 2-fold increase in IP4 was seen with 5.0 mM Ca2+ only after 15 min. Fluoride ion generated a dose-dependent increase in IP4, with a 48% rise at 10 mM F-, presumably by activating phospholipase-C through a guanine nucleotide regulatory (G) protein-dependent process. We conclude that inositol 1,4,5-trisphosphate generated in response to high extracellular Ca2+ and Mg2+ concentrations can be converted to IP4 in parathyroid cells. The slow kinetics for the increase in IP4 with high Ca2+ in the absence of Li+, however, do not support a role for IP4 in the early phase of the sustained increase in cytosolic Ca2+ produced by high extracellular Ca2+ concentrations.