Activation of Adenosine 3',5'-Monophosphate-Dependent Protein Kinase in Normal and Malignant Bone Cells by Parathyroid Hormone, Prostaglandin E2, and Prostacyclin*

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Abstract
Hormonal activation of cAMP-dependent protein kinase has been studied in cultured cells derived from a rat osteogenic sarcoma and in osteoblast-rich cells grown from newborn rat calvaria. Both cell strains contain adenylate cyclase activities which respond to parathyroid hormone (PTH) and a variety of prostanoids. PTH, prostaglandin E 2 (PGE 2), and prostacyclin (PGI 2) were all capable of activating cAMP-dependent protein kinase (s) in suspensions of the two cell types. Activation was very rapid in all cases, being detectable at 10 sec and maximal between 30–60 sec. Using saturating concentrations of hormones, the protein kinase activity ratio remained elevated (between 0.6–0.9) for up to 35 min after the start of PGE 2 stimulation, but declined toward basal activity ratio 5–10 min after stimulation with PTH or PGI2. Each of the hormones caused a dose-dependent increase in activation of cAMP-dependent protein kinase in both cell types. Half-maximal activation of the enzyme occurred at 2 × 10 -9 M bovine PTH for calvarial cells, at 10-8 M bPTH for osteogenic sarcoma cells, and at 2–4 × 10-8 M PGE22 and 1–3 × 10-7 M PGI22 for both cell types. Maximal activation of protein kinase occurred before maximal cAMP accumulated, implying that only a fraction of cAMP is biologically significant. These two cell strains provide a useful means of analyzing postreceptor events in the hormonal regulation of bone cells.

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