Different roles for calcium and cyclic AMP in the action of PTH: Studies in bone explants and isolated bone cells

• Published in: Bone (New York, N.Y.) Vol. 9; no. 2; pp. 93 - 100
• Main Authors: Herrmann-Erlee, M.P.M., Van Der Meer, J.M., Löwik, C.W.G.M., Van Leeuwen, J.P.T.M., Boonekamp, P.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 1988
• Subjects: Animals; Bone and Bones - metabolism; Bone Cells; Bone Explants; Bone Resorption - metabolism; Bone Resorption - physiopathology; Calcimycin - pharmacology; Calcium - metabolism; cAMP; Cells, Cultured; Colforsin - pharmacology; Cyclic AMP - metabolism; Cytoplasm - metabolism; Dose-Response Relationship, Drug; Egtazic Acid - pharmacology; Fetus; intracellular Ca 2; Mice; Nifedipine - pharmacology; Parathyroid Hormone; Parathyroid Hormone - physiology; Rats; Skull; Verapamil - pharmacology; intracellular Ca 2; Bone Explants; Bone Cells; cAMP; Parathyroid Hormone
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/8756-3282(88)90109-3

In fetal mouse calvaria forskolin (0.1–100 μM), like PTH, stimulated cyclic AMP production in a dose-dependent way. The dose-response curve for forskolin-induced bone mineral release (24 hrs), however, demonstrated a biphasic character, showing stimulation at 0.1 μM and inhibition at 5 and 10 μM. In addition, forskolin-stimulated bone resorption reached a plateau after 48 hrs of incubation, a phenomenon which did not occur with PTH. Forskolin (0.1 μM) strongly stimulated PTH-induced cyclic AMP production in fetal mouse calvaria. However, PTH-stimulated bone resorption and PTH-induced increase in cytosolic free Ca 2+ in bone fetal rat cells were not stimulated by forskolin (0.1 μM). 9-(Tetrahydro-2-furyl) adenine (100 μM) completely blunted PTH-stimulated cyclic AMP response in fetal mouse calvaria. PTH-stimulated bone resorption was also completely inhibited, but only after 6 hrs and not after 24 hrs of incubation. With nifedipine and varabamil PTH-stimulated bone resorption was significantly inhibited after 24 hrs of incubation and not significantly after 6 hrs of incubation. A23187 (1 gmM) significantly stimulated PTH-stimulated cyclic AMP level and increased basal cytosolic free Ca 2+ concentration in cultured rat bone cells. In calvaria, however, it had no effect on either basal and PTH-stimulated cyclic AMP production or on basal and PTH-stimulated bone resorption (6 and 24 hrs). From these observations it follows that in calvaria manipulation of intracellular cyclic AMP only (partially) affects bone resorption. This observation points to a role for an additional second messenger in establishing full blown bone resorption. Some of the results are published in short elsewhere.