Eicosanoids are released by bone cells in response to physical, hormonal, and cytokine stimulation, and they can both inhibit and stimulate bone formation. We investigated the effect of PGE2 on sodium-dependent phosphate (Na(d)Pi) transport in a rat bone-derived cell line, PyMS. PGE2 and 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C, increased Na(d)Pi uptake in a dose- and time-dependent manner. There was no change in Na-dependent alanine transport, and the effects of PGE2 and TPA were not associated with corresponding changes in cell number or protein content. Their effects on Na(d)Pi uptake were not additive. Calphostin C, an inhibitor of protein kinase C (10(-8) M) completely blocked TPA- and PGE2-stimulated Na(d)Pi uptake. The results are consistent with a crucial role of protein kinase C activation in the short term stimulation of Na(d)Pi transport by PGE2 in PyMS cells.