Gallium nitrate is an effective antihypercalcemic and antiresorptive agent. Although
its effects on osteoclasts are well documented, the mechanism of action of gallium
nitrate on osteoblasts is still not established. To determine the effects of gallium
nitrate on calcium signalling, we studied its effects on intracellular calcium concentration
in UMR-106 rat osteoblastic osteosarcoma cell line. Cells were loaded with a calcium
binding fluorescent dye, fluo-3. Changes in fluorescence reflected changes in cytosolic
calcium. Gallium nitrate elicited a dose-dependent biphasic calcium transient with
an initial decrease followed by an increase, and these changes were seen at high extracellular
calcium concentration. Markedly altered signal was seen in nominal calcium-free medium,
suggesting that gallium nitrate mobilized calcium only partly from intracellular stores.
Gallium nitrate, at concentrations as low as 3 μg/ml, inhibited parathyroid hormone-
stimulated calcium transients. High doses of parathyroid hormone could overcome this
inhibition. This inhibitory effect appears to be selective, since gallium nitrate
did not prevent calcium transients elicited by α- thrombin or prostaglandin F(1α).
Failure of gallium nitrate to prevent calcium transients elicited by these agents,
even after the inhibition of parathyroid hormone-induced signal, indicates that the
inhibition is not a toxic effect. In conclusion, gallium nitrate has a marked effect
on calcium signalling in UMR-106 cells that might be of major importance in modifying
the effects of calcemic hormones or local factors on osteoblasts.