title: Forskolin mimics the effects of calcitonin but not parathyroid hormone on bone resorption in vitro.
abstract: Parathyroid hormone (PTH) and calcitonin stimulate bone adenylate cyclase activity and increase bone cAMP content, but PTH enhances and calcitonin inhibits bone resorption. This study examined the effects of forskolin, a non-hormonal activator of adenylate cyclase, on bone resorption and cAMP accumulation in 19-day fetal rat limb bones. Forskolin (10(-9) to 10(-5) M) stimulated bone cAMP generation in a concentration-dependent manner. However, in contrast to bPTH(1-34), which also stimulated cAMP accumulation, forskolin did not stimulate bone resorption. Moreover, forskolin did not augment the bone-resorbing activity of PTH even though it potentiated PTH stimulation of bone cAMP levels. Rather, high doses of forskolin (10(-6) to 10(-5) M) exhibited a calcitonin-like effect to inhibit PTH-mediated bone resorption. These results support a second-messenger function of cAMP for the inhibitory effects of calcitonin, but not for the stimulatory effects of PTH on bone resorption.
authors.affiliation: Endocrine Unit, Veterans Administration Medical Center, San Francisco, CA.
authors.forename: R F
authors.initials: RF
authors.lastname: Klein
authors.forename: R A
authors.initials: RA
authors.lastname: Nissenson
authors.forename: G J
authors.initials: GJ
authors.lastname: Strewler
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D005552:Forelimb / Q000196:embryology / Q000502:physiology; D007700:Kinetics; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002132:Calcium Radioisotopes; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C025076:parathyroid hormone (1-34), bovine; D005576:Colforsin; D002116:Calcitonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases