Kano J, Sugimoto T, Fukase M, Fujita T
Department of Medicine, Kobe University School of Medicine, Japan.
Biochem Biophys Res Commun. 1991 May 31;177(1):365-9. doi: 10.1016/0006-291x(91)91992-l.
In order to characterize the direct involvement of cAMP in the change of osteoblast proliferation by parathyroid hormone (PTH), we employed the diastereoisomers of adenosine 3',5'-cyclic phosphorothioate, Sp-cAMPS and Rp-cAMPS, which have been recently shown to act directly as agonist and antagonist, respectively in the activation of cAMP-dependent protein kinase (PKA). Dibutyryl cAMP (dbcAMP) and cholera toxin as well as human(h) PTH-(1-34) significantly inhibited [3H]thymidine incorporation (TdR) in osteoblastic osteosarcoma cells, UMR-106. Sp-cAMPS (10(-6)-10(-4) M) inhibited TdR in a dose-dependent manner. Although Rp-cAMPS (10(-6)-10(-4) M) itself did not affect TdR, it significantly blocked dbcAMP-, cholera toxin- and Sp-cAMPS-induced suppression of TdR. Moreover, Rp-cAMPS (10(-6)-10(-4) M) dose-dependently antagonized hPTH-induced suppression of TdR. Present studies first indicated that the activation of PKA is directly linked to the change of osteoblast proliferation by PTH.
为了明确环磷酸腺苷（cAMP）在甲状旁腺激素（PTH）引起的成骨细胞增殖变化中的直接作用，我们使用了3'，5'-环磷硫腺苷的非对映异构体，即Sp-cAMPS和Rp-cAMPS，最近的研究表明它们分别作为激动剂和拮抗剂直接作用于cAMP依赖性蛋白激酶（PKA）的激活。二丁酰环磷腺苷（dbcAMP）、霍乱毒素以及人（h）PTH-（1-34）显著抑制成骨肉瘤细胞UMR-106中的[3H]胸腺嘧啶核苷掺入（TdR）。Sp-cAMPS（10^-6 - 10^-4 M）以剂量依赖性方式抑制TdR。虽然Rp-cAMPS（10^-6 - 10^-4 M）本身不影响TdR，但它能显著阻断dbcAMP、霍乱毒素和Sp-cAMPS诱导的TdR抑制。此外，Rp-cAMPS（10^-6 - 10^-4 M）以剂量依赖性方式拮抗hPTH诱导的TdR抑制。目前的研究首次表明，PKA的激活与PTH引起的成骨细胞增殖变化直接相关。
