Bradykinin is recognized to be involved in the process of bone resorption in chronic inflammatory diseases. We previously reported that prostaglandin E
2 (PGE
2), known as a potent bone resorbing agent, induces phosphoinositide hydrolysis, cAMP production and Ca
2+ influx in osteoblast-like MC3T3-E1 cells, and these dose-dependencies are different to one another. To clarify the signaling mechanism of bradykinin, we compared the intracellular signaling system of bradykinin with that of PGE
2 in these cells. Bradykinin stimulated Ca
2+ influx dose-dependently in the range between 0.1nM and 0.1μM even in the presence of nifedipine, a Ca
2+ antagonist that inhibits the voltage-dependent L-type Ca
2+ channel. The maximum effect of bradykinin (0.1μM) on Ca
2+ influx was almost as great as that of PGE
2 (0.5μM). Bradykinin had little effect on cAMP accumulation, while PGE
2 significantly stimulated it. Bradykinin stimulated the formation of inositol phosphates much less strongly than PGE
2. Bradykinin stimulated inositol 1, 4, 5-trisphosphate [Ins(1, 4, 5)P
3] formation dose-dependently between 0.1nM and 0.1μM, and the dose-dependent curves of bradykinin-induced Ca
2+ influx and Ins(1, 4, 5)P
3 were similar. However, the maximum effect of PGE
2 (10μM) on Ins (1, 4, 5) P
3 formation was about 2-fold higher than that of bradykinin (0.1μM). These results suggest that bradykinin induces Ca
2+ influx independent of the voltage-dependent L-type Ca
2+ channel and phosphoinositide hydrolysis in a similar dose-dependent manner in osteoblast-like cells.
View full abstract