Role of calcium and cAMP in heterologous up-regulation of the 1,25-dihydroxyvitamin D3 receptor in an osteoblast cell line.
To understand further the mechanism of action of parathyroid hormone (PTH) in the stimulation of the number of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) binding sites in UMR 106-01 cells we studied the role of cAMP and calcium. In addition to PTH other agents known to act via the cAMP signal pathway, prostaglandin E2, forskolin and dibutyryl cAMP, caused an increase in 1,25(OH)2D3 binding. Addition of the adenylate cyclase inhibitor 9-(tetrahydro-2-furyl)adenine resulted in a marked decrease of PTH-stimulated cAMP production but this was not followed by a reduction of 1,25(OH)2D3 receptor up-regulation by PTH. Increasing the intracellular calcium concentration by Bay K 8644 and A23817 independent of an activation of the cAMP signal pathway did not result in an increased 1,25(OH)2D3 binding. The calcium channel blockers nitrendipine and verapamil and chelating extracellular calcium with EGTA all reduced cAMP-mediated stimulation of 1,25(OH)2D3 binding. This reduction was not due to a reduce cAMP production as verapamil even potentiated PTH- and forskolin-stimulated cAMP production in a dose-dependent manner. The present study provides evidence for an interrelated action of calcium and cAMP in the heterologous up-regulation of the 1,25(OH)2D3 receptor. The current data show an interaction between the cAMP and calcium signal pathway at (1) the level of cAMP generation/degradation, and (2) a level located distal in the cascade leading to 1,25(OH)2D3 receptor up-regulation.
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
J P
JP
van Leeuwen
J C
JC
Birkenhäger
J P
JP
Schilte
C J
CJ
Buurman
H A
HA
Pols
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D014700:Verapamil; D000242:Cyclic AMP; D002117:Calcitriol; D000225:Adenine; D015232:Dinoprostone; D002118:Calcium