Pols H A, Schilte H P, Herrmann-Erlee N M, Visser T J, Birkenhäger J C
Department of Internal Medicine III, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Bone Miner. 1986 Oct;1(5):397-405.
1,25(OH)2D3 induced a dose-dependent increase of alkaline phosphatase activity in primary cultures of fetal rat osteoblast-like cells. A slight decrease in final DNA content was found in densely seeded cultures and at 10(-8) M 1,25(OH)2D3 only. Furthermore, 1,25(OH)2D3 treatment resulted in an attenuation of the cAMP response to PTH without an effect on the EC50 of PTH. On the other hand no change of the cAMP response to forskolin was observed. Forskolin partly restored the decline in the PTH-stimulated adenylate cyclase activity. The results indicate that physiological concentrations of 1,25(OH)2D3 have a stimulatory effect on the alkaline phosphatase of osteoblast-like cells and decrease the responsiveness of these cultures to PTH. We propose that the site of action of 1,25(OH)2D3 in the adenylate cyclase system is either at the level of the regulatory unit or on the interaction of the regulatory with the catalytic unit.
1,25(OH)₂D₃在原代培养的胎鼠成骨细胞样细胞中诱导碱性磷酸酶活性呈剂量依赖性增加。在高密度接种的培养物中以及仅在10⁻⁸ M 1,25(OH)₂D₃时,最终DNA含量略有下降。此外,1,25(OH)₂D₃处理导致对甲状旁腺激素(PTH)的cAMP反应减弱,但对PTH的半数有效浓度(EC₅₀)没有影响。另一方面,未观察到对福斯高林的cAMP反应有变化。福斯高林部分恢复了PTH刺激的腺苷酸环化酶活性的下降。结果表明,生理浓度的1,25(OH)₂D₃对成骨细胞样细胞的碱性磷酸酶有刺激作用,并降低这些培养物对PTH的反应性。我们提出,1,25(OH)₂D₃在腺苷酸环化酶系统中的作用位点要么在调节单位水平,要么在调节单位与催化单位的相互作用上。