Different roles for calcium and cyclic AMP in the action of PTH: studies in bone explants and isolated bone cells.
In fetal mouse calvaria forskolin (0.1-100 microM), 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 microM and inhibition at 5 and 10 microM. 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 microM) 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 microM). 9-(Tetrahydro-2-furyl) adenine (100 microM) 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 microM) 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.
Herrmann-Erlee
M P
MP
Laboratory of Cell Biology and Histology, University of Leiden, The Netherlands.
van der Meer
J M
JM
Löwik
C W
CW
van Leeuwen
J P
JP
Boonekamp
P M
PM
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000503:physiopathology; D001842:Bone and Bones / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005333:Fetus; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats; D012886:Skull; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D005576:Colforsin; D000001:Calcimycin; D004533:Egtazic Acid; D014700:Verapamil; D000242:Cyclic AMP; D009543:Nifedipine; D002118:Calcium