Delayed stimulatory effect of cyclic AMP on bone resorption in vitro.
The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96-114 h using half calvaria from 6-7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013806:Theophylline / Q000378:metabolism
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D003994:Bucladesine; D013806:Theophylline; D015056:1-Methyl-3-isobutylxanthine