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Forskolin has both stimulatory and inhibitory effects on bone resorption in fetal rat long bone cultures
Author(s) -
Lorenzo Joseph A.,
Sousa Sandra,
Quinton Joy
Publication year - 1986
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650010403
Subject(s) - forskolin , endocrinology , medicine , ibmx , bone resorption , adenosine , cyclase , resorption , cyclic adenosine monophosphate , adenylate kinase , chemistry , phosphodiesterase , parathyroid hormone , phosphodiesterase inhibitor , biology , calcium , enzyme , biochemistry , stimulation , receptor
The diterpene forskolin which increases 3′,5′‐cyclic adenosine monophosphate concentrations (cAMP) in intact cells by directly activating the enzyme adenyl cyclase, was examined for its ability to alter bone resorption in fetal rat long bone cultures. After 48 h, forskolin inhibited resorption at 1.0 and 10 μ However, after 120 h, it had a small stimulatory effect at 1.0 μ M and no net effect on resorption at 10 μ Isobutylmethylxanthine (IBMX), which elevates cAMP levels in cells by inhibiting the enzyme 3′,5′‐cyclic adenosine monophosphate phosphodiesterase, produced a resorptive response which was slightly different from that of forskolin. After both 48 and 120 h, IBMX at 0.1 m M stimulated resorption while at 1.0 m M , it had only inhibitory effects. In bones which were stimulated to resorb with either parathyroid hormone or 1,25(OH) 2 vitamin D, forskolin inhibited resorption. The inhibitory effects of forskolin on hormonally stimulated resorption were transient in cultures treated with 1.0 μ M but were sustained with 10 μ M . Inhibitory responses to forskolin did not appear to result from toxicity since they were completely reversed when forskolin was removed from the media. These results imply that agents which increases 3′,5′‐cyclic adenosine monophosphate concentrations in bone activate two resorptive pathways: one which is inhibitory and another which is stimulatory.