Effects of forskolin on bone in organ culture.

The effects of forskolin, which directly activates adenylate cyclase in most systems, have been compared with the actions of parathyroid hormone and calcitonin, both of which have been suggested to utilize cAMP as a second messenger in their actions on bone. Forskolin alone stimulated calcium release from neonatal mouse calvaria and fetal rat limb bones in vitro in a dose-dependent manner. The effect was maximal at 10(-6) M in both systems. At higher concentrations forskolin completely inhibited stimulated bone resorption, although with submaximal concentrations the inhibition was only partially sustained up to 72 h. Forskolin directly stimulated cAMP release from calvaria into the medium at concentrations up to 10(-4) M. Forskolin had no effect on the interaction between parathyroid hormone and calcitonin, while calcitonin inhibited the stimulatory effect of forskolin comparably with its inhibition of parathyroid hormone-stimulated bone resorption. The results indicate that forskolin has dual effects on bone and can mimic responses of both parathyroid hormone and calcitonin in both bone culture systems. The observed response depends on the concentration of forskolin used and the length of treatment with the drug.