A revised role for cyclic AMP in prostaglandin-induced bone resorption.
The effect of cyclic AMP on bone resorption produced by prostaglandin E1 (PGE1) and E2 (PGE2) was studied using 6--7 day-old murine calvarial bones cultured in a chemically defined medium for 48 h. Dibutyryl cyclic AMP inhibited in a dose-related way the prostaglandin-induced mobilization of 45Ca from prelabelled bones. The phosphodiesterase inhibitors, theophylline and 3-isobutyl-methylxanthine, also reduced the release of 45Ca induced by the prostaglandins. It was also found that the doses of the later phosphodiesterase inhibitor needed to inhibit prostaglandin-stimulated mineral mobilization were lower than those needed to reduce unstimulated resorption. The mechanism behind the inhibitory effect of cAMP on prostaglandin-induced bone resorption is unknown, but might be related to the capacity of cAMP to inhibit prostaglandin-stimulated release of lysosomal enzymes, which was also demonstrated in this study.
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D000242:Cyclic AMP / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005966:Glucuronidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D011459:Prostaglandins E, Synthetic; D003994:Bucladesine; D000242:Cyclic AMP; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D002118:Calcium