Parathyroid hormone-stimulated resorption in calvaria cultured in serum-free medium is enhanced by the calcium-mobilizing activity of 1,25-dihydroxyvitamin D(3).
1,25(OH)(2)D(3) enhances parathyroid hormone (PTH)-induced Ca(2+) signaling in osteoblasts by activating plasma membrane voltage-sensitive Ca(2+) channels (VSCCs). The ability of 1,25(OH)(2)D(3) or the VSCC-activating analog AT (25-hydroxy-16-ene-23-yne-D(3)) to enhance parathyroid hormone-stimulated (45)Ca(2+) release from cultured new-born rat calvaria was measured. Analog BT (1,24-dihydroxy-22-ene-24-cyclopropyl-D(3)), that does not mobilize Ca(2+), also was tested along with PTH. Control experiments were performed with and without PTH and with and without serum. Individual calvaria labeled in utero with (45)Ca(2+) were cultivated in serum-free medium on filters at the medium/air interface of 24-well culture plates and (45)Ca(2+) release followed over 72 h. The results demonstrated that 1,25(OH)(2)D(3) and the Ca(2+)-mobilizing analog, AT, but not the nuclear receptor-binding analog, BT, enhanced PTH-stimulated (45)Ca(2+) release under serum-free conditions. This enhancement effect of the seco-steroids was not evident in the presence of 10% fetal calf serum. The effect of analog AT was faster than that of 1,25(OH)(2)D(3). Nitrendipine, a specific L-type VSCC blocker, attenuated enhancement by vitamin D compounds, indicating that the high-threshold L-type VSCC is a molecular transducer of costimulation. These results emphasize the synergy between the calcitropic hormones 1,25(OH)(2)D(3) and PTH in cultures containing osteoblasts and osteoclasts, and suggest that the Ca(2+)-mobilizing activity of 1,25(OH)(2)D(3) enhances Ca(2+) release from bone.
Li
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Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Farach-Carson
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MC
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005333:Fetus / Q000166:cytology; D009568:Nitrendipine / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000166:cytology*
C116776:25-hydroxy-16,23-diene vitamin D3; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D016895:Culture Media, Serum-Free; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D009568:Nitrendipine; D002117:Calcitriol; D002118:Calcium