Forskolin-induced bone resorption in neonatal mouse calvaria in vitro.

The role of cyclic adenosine 3',5'-monophosphate (cAMP) in inducing bone resorption was studied in neonatal mouse calvaria in vitro. Forskolin, a stimulator of adenylate cyclase, increased the medium calcium concentration at 96 hr of incubation, indicating enhanced bone resorption. Bone resorption was observed between 1 X 10(-4) and 1 X 10(-6) M forskolin; the maximal effect was at 1 X 10(-5) M and there was no effect at 1 X 10(-7) M. Lactic acid release was increased during the 96 hr of incubation in proportion to the calcium release in the media. The bone acid phosphatase activity was increased and the alkaline phosphatase activity was decreased. Bone carbonic anhydrase activity was increased more than twofold. Forskolin-induced bone resorption was significantly but incompletely inhibited by 10(-4) M acetazolamide, a carbonic acid anhydrase inhibitor. These findings support the concept that carbonic anhydrase plays a significant role in bone resorption.