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.