The effects of 1,25-dihydroxyvitamin D3 on growth, alkaline phosphatase and adenylate cyclase of rat osteoblast-like cells.
1,25(OH)2D3 induced a dose-dependent increase of alkaline phosphatase activity in primary cultures of fetal rat osteoblast-like cells. A slight decrease in final DNA content was found in densely seeded cultures and at 10(-8) M 1,25(OH)2D3 only. Furthermore, 1,25(OH)2D3 treatment resulted in an attenuation of the cAMP response to PTH without an effect on the EC50 of PTH. On the other hand no change of the cAMP response to forskolin was observed. Forskolin partly restored the decline in the PTH-stimulated adenylate cyclase activity. The results indicate that physiological concentrations of 1,25(OH)2D3 have a stimulatory effect on the alkaline phosphatase of osteoblast-like cells and decrease the responsiveness of these cultures to PTH. We propose that the site of action of 1,25(OH)2D3 in the adenylate cyclase system is either at the level of the regulatory unit or on the interaction of the regulatory with the catalytic unit.
Pols
H A
HA
Department of Internal Medicine III, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Schilte
H P
HP
Herrmann-Erlee
N M
NM
Visser
T J
TJ
Birkenhäger
J C
JC
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats
D010281:Parathyroid Hormone; D005576:Colforsin; D004247:DNA; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D000262:Adenylyl Cyclases; D002117:Calcitriol