Differential Effect of TPA on PGE 2 and Cicaprost-Induced cAMP Synthesis in UMR-106 cells

Abstract

PGE 2 and prostacyclin each enhance cAMP synthesis in the osteoblast-like cell line UMR-106. The amount of cAMP induced by PGE 2 was 5–7-fold greater than the amount induced by cicaprost or iloprost, stable prostacyclin analogues. Both PGE 2 and the two prostacyclin analogues enhanced cAMP synthesis with similar time dependence. The EC 50 values of PGE 2 and cicaprost were 3×10 −6 and 5×10 −8 M, respectively. Short-term incubation of the cells with 12- o-tetradecanoylphorbol 13-acetate (TPA) markedly reduced the PGE2-induced cAMP synthesis. In contrast, cells that were incubated with the same concentrations of TPA in the presence of cicaprost or iloprost showed a 1.6-fold increase in cAMP formation. The marked disparity between the cAMP response to cicaprost and PGE2 in the presence of TPA suggests that the two prostanoids induce cAMP synthesis in the UMR-106 cells by interaction with different receptors. These observations support the idea that the osteoblastic UMR-106 cells may express specific prostacyclin receptors and suggest that prostacyclin may have a unique role in osteoblasts.