Effects of high extracellular calcium and strontium on inositol polyphosphates in bovine parathyroid cells.

The addition of Ca2+ or a variety of divalent cations increases intracellular Ca2+ in parathyroid cells and suppresses secretion. Since 1,4,5-inositol trisphosphate (IP3) and 1,3,4,5-inositol tetrakisphosphate (IP4) mediate Ca2+ mobilization in other systems, we examined high Ca(2+)- and Sr(2+)-induced accumulation of IP3 and IP4 isomers by anion-exchange HPLC and measured 1,4,5-IP3 mass in parathyroid cells. Raising extracellular [Ca2+] from 0.5 to 3.0 mM increased 3H-1,4,5-IP3 within 5 s, which was confirmed by mass measurements. 3H-1,3,4-IP3 rose gradually by 10 s and increased for 60 s after the addition of Ca2+. Although we detected no change in 3H-1,3,4,5-IP4, the increase in 3H-1,3,4-IP3 suggests that 3H-1,3,4,5-IP4 was being formed. The addition of 4 mM SrCl2 produced similar changes in 1,4,5-IP3, which were confirmed by mass assay. 3H-1,3,4,5-IP4 did not change. However, Sr2+ induced a gradual increase in 3H-1,3,4-IP3, which remained above control levels for 5 minutes. Isotopic labeling studies in this system may underestimate changes in 1,4,5-IP3 mass, but both mass and radioisotopic analyses indicate that high extracellular Ca2+ and Sr2+ stimulate substantial increases in 1,4,5-IP3 without significant accumulation of 1,3,4,5-IP4. These studies suggest a role for 1,4,5-IP3 in intracellular Ca2+ mobilization by divalent cations in parathyroid cells.