Stimulation by parathyroid hormone-related protein and transforming growth factor-alpha of phosphate transport in osteoblast-like cells.
Parathyroid hormone (1-34) [PTH-(1-34)] has been shown to stimulate sodium-dependent phosphate transport (NaPiT) in UMR-106 osteoblast-like cells through a cAMP-dependent mechanism. Whether a synthetic amino-terminal fragment of parathyroid hormone-related protein (PTHrP) or the full-length molecule, which are recognized to interact with the same receptor as PTH, affect NaPiT in the same way is not known. We investigated and compared the effects of bPTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) on NaPiT and cAMP production in the osteoblastic cell line UMR-106. Each of the three peptides increased cAMP production and exerted a concentration-dependent stimulation of NaPiT after incubation for 4-6 h. We also studied the effect of transforming growth factor-alpha (TGF-alpha), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-alpha-induced modulation of the response to PTHrP or PTH. TGF-alpha caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-alpha attenuated cAMP production stimulated by PTH, PTHrP-(1-34), or PTHrP-(1-141). PTHrP or PTH did not further increase NaPiT in TGF-alpha-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-alpha increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.
Pizurki
L
L
Department of Medicine, University Hospital of Geneva, Switzerland.
Rizzoli
R
R
Caverzasio
J
J
Bonjour
J P
JP
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009363:Neoplasm Proteins / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010710:Phosphates; D011506:Proteins; D016211:Transforming Growth Factor alpha; C066078:parathyroid hormone-related protein (1-141); C054296:parathyroid hormone-related protein (1-34); C025076:parathyroid hormone (1-34), bovine; D000242:Cyclic AMP; D000409:Alanine