The activation of cAMP-dependent protein kinase is directly linked to the stimulation of bone resorption by parathyroid hormone.
The present study was performed to characterize the direct involvement of cAMP in the stimulation of bone resorption by parathyroid hormone (PTH), using Sp-cAMPS and Rp-cAMPS, which were the direct agonist and antagonist in the activation of cAMP-dependent protein kinase (PKA), respectively. Bone resorbing activity was estimated as the number of pits formed on the dentine slice and total area of pits per slice in bone marrow cells derived from 2 week-old mice. Dibutyryl cAMP (dbcAMP)(10(-4)M) and Sp-cAMPS (10(-4)M) caused the remarkable stimulation of bone resorption. Although Rp-cAMPS (10(-4)M) did not affect bone resorption by itself, it significantly inhibited dbcAMP- and Sp-cAMPS-induced stimulation of bone resorption. Moreover, Rp-cAMPS (10(-4)M) antagonized 10(-7)M human PTH-(1-34)-induced stimulation of bone resorption, although it did not affect 10(-8)M 1,25(OH)2D3-induced stimulation of bone resorption. Present study indicates the direct involvement of PKA in the stimulation of bone resorption by PTH.
Kaji
H
H
Department of Medicine, Kobe University School of Medicine, Japan.
Sugimoto
T
T
Kanatani
M
M
Fukase
M
M
D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D019379:Teriparatide; D013873:Thionucleotides / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D019379:Teriparatide; C016957:adenosine-3',5'-cyclic phosphorothioate; D003994:Bucladesine; D000242:Cyclic AMP; D011494:Protein Kinases; D002117:Calcitriol