AJP - Endocrinology and Metabolism, Vol 252, Issue 1 E44-E48, Copyright © 1987 by American Physiological Society
Effects of forskolin on bone in organ culture
N. S. Krieger and P. H. Stern
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.
