We investigated the effects of vitamin D3 on the signaling pathways by prostaglandin E2 (PGE2) in osteoblast‐like MC3T3‐E1 cells. The pretreatment with 1,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3), an active form of vitamin D3, significantly inhibited cAMP accumulation induced by 10 μM PGE2 in a dose‐dependent manner in the range between 1 pM and 1 nM. This effect of 1,25‐(OH)2D3 was dependent on the time of pretreatment up to 8 h. 1,25‐(OH)2D3 also inhibited the cAMP accumulation induced by NaF, a GTP‐binding protein activator, or forskolin which directly activates adenylate cyclase. On the other hand, 1,25‐(OH)2D3 significantly inhibited PGE2‐induced IP3 formation in a dose‐dependent manner between 10 pM and 1 nM. However, 1,25‐(OH)2D3 had little effect on NaF‐induced IP3 formation. The pretreatment with 24,25‐dihydroxyvitamin D3, an inactive form of vitamin D3, affected neither cAMP accumulation nor IP3 formation induced by PGE2. These results strongly suggest that 1,25‐(OH)2D3 modulates the signaling by PGE2 in osteoblast‐like cells as follows: the inhibitory effect on the cAMP production is exerted at a point downstream from adenylate cyclase and the inhibitory effect on the phosphoinositide hydrolysis is exerted at the point between the PGE2 receptor and GTP‐binding protein, probably Gi2.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology