The activation of cAMP-dependent protein kinase is directly linked to the regulation of osteoblast proliferation (UMR-106) by parathyroid hormone.
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.
Kano
J
J
Department of Medicine, Kobe University School of Medicine, Japan.
Sugimoto
T
T
Fukase
M
M
Fujita
T
T
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D004789:Enzyme Activation; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D019379:Teriparatide; D013873:Thionucleotides / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D013873:Thionucleotides; D019379:Teriparatide; C016957:adenosine-3',5'-cyclic phosphorothioate; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases