The cyclic-AMP antagonist adenosine-3',5'-cyclic monophosphosphorothioate, RP-isomer inhibits parathyroid hormone induced bone resorption, in vitro.

Abstract	Stimulation of osteoclastic bone resorption is mediated via the osteoblasts. In order to investigate the second messenger events that cause the osteoblasts to initiate bone resorption we have evaluated the effect of the cyclic AMP antagonist adenosine-3'5'-cyclic monophosphosphorothioate, Rp-isomer (Rp-cAMPS) on bone resorption in vitro, by measuring the release of prelabelled 45Ca from cultured neonatal mouse calvarial bones. Forskolin (FSK, at and above 10 nM), an agent that enhances cyclic AMP-formation, stimulated bone resorption in 96 h cultures. Addition of Rp-cAMPS to the incubation media dose-dependently inhibited bone resorption induced by FSK (0.5 microM), with total inhibition obtained at 30 microM Rp-cAMPS. Bone resorption stimulated by parathyroid hormone (PTH, 0.1-10 nM, 72 h) was also inhibited by Rp-cAMPS (30 microM), while bone resorption induced by 1.25(OH)2D3 (1-10 nM, 72 h) was unaffected by Rp-cAMPS. These data demonstrate that PTH and 1,25(OH)2D3 cause bone resorption via different mechanisms and that cyclic AMP is the major second messenger in PTH-induced bone resorption.
Authors	O Ljunggren, S Ljunghall
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 193 Issue 3 Pg. 821-6 (Jun 30 1993) ISSN: 0006-291X [Print] United States
PMID	8391806 (Publication Type: Journal Article)
Chemical References	Parathyroid Hormone-Related Protein Peptide Fragments Protein Kinase Inhibitors Proteins Thionucleotides parathyroid hormone-related protein (1-34) Colforsin adenosine-3',5'-cyclic phosphorothioate Cyclic AMP Calcitriol Calcium
Topics	Animals Animals, Newborn Bone Resorption Bone and Bones (cytology, drug effects, physiology) Calcitriol (pharmacology) Calcium (metabolism) Cells, Cultured Colforsin (pharmacology) Cyclic AMP (analogs & derivatives, pharmacology) Dose-Response Relationship, Drug Humans Isomerism Kinetics Mice Parathyroid Hormone-Related Protein Peptide Fragments (antagonists & inhibitors, pharmacology) Protein Kinase Inhibitors Proteins (antagonists & inhibitors, pharmacology) Thionucleotides (pharmacology)

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