TY - JOUR
T1 - Different roles for calcium and cyclic AMP in the action of PTH
T2 - Studies in bone explants and isolated bone cells
AU - Herrmann-Erlee, M. P.M.
AU - Van Der Meer, J. M.
AU - Löwik, C. W.G.M.
AU - Van Leeuwen, J. P.T.M.
AU - Boonekamp, P. M.
PY - 1988
Y1 - 1988
N2 - 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 Ca2+ 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 Ca2+ 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.
AB - 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 Ca2+ 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 Ca2+ 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.
UR - http://www.scopus.com/inward/record.url?scp=0023904092&partnerID=8YFLogxK
U2 - 10.1016/8756-3282(88)90109-3
DO - 10.1016/8756-3282(88)90109-3
M3 - Article
C2 - 2841959
AN - SCOPUS:0023904092
SN - 8756-3282
VL - 9
SP - 93
EP - 100
JO - Bone
JF - Bone
IS - 2
ER -