Intracellular Signaling Mechanism of Bradykinin in Osteoblast-Like Cells

Endocrine Journal

HARUHIKO TOKUDA²  JUN KOTOYORI²  YUTAKA OISO²  OSAMU KOZAWA¹ 

[1] Department of Biochemistry, Institute for Developmental Research;First Department of Internal Medicine, Nagoya University School of Medicine

关键词: Bradykinin;    Prostaglandin E2;    Phosphoinositide;    Calcium;    Osteoblast;   

DOI  :  10.1507/endocrj.41.189

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(26)Cited-By(4)Bradykinin is recognized to be involved in the process of bone resorption in chronic inflammatory diseases. We previously reported that prostaglandin E2 (PGE2), known as a potent bone resorbing agent, induces phosphoinositide hydrolysis, cAMP production and Ca2+ 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 PGE2 in these cells. Bradykinin stimulated Ca2+ influx dose-dependently in the range between 0.1nM and 0.1μM even in the presence of nifedipine, a Ca2+ antagonist that inhibits the voltage-dependent L-type Ca2+ channel. The maximum effect of bradykinin (0.1μM) on Ca2+ influx was almost as great as that of PGE2 (0.5μM). Bradykinin had little effect on cAMP accumulation, while PGE2 significantly stimulated it. Bradykinin stimulated the formation of inositol phosphates much less strongly than PGE2. Bradykinin stimulated inositol 1, 4, 5-trisphosphate [Ins(1, 4, 5)P3] formation dose-dependently between 0.1nM and 0.1μM, and the dose-dependent curves of bradykinin-induced Ca2+ influx and Ins(1, 4, 5)P3 were similar. However, the maximum effect of PGE2 (10μM) on Ins (1, 4, 5) P3 formation was about 2-fold higher than that of bradykinin (0.1μM). These results suggest that bradykinin induces Ca2+ influx independent of the voltage-dependent L-type Ca2+ channel and phosphoinositide hydrolysis in a similar dose-dependent manner in osteoblast-like cells.

【 授权许可】

Unknown