Effect of dexamethasone on parathyroid hormone (PTH) and PTH-related protein regulated phosphate uptake in opossum kidney cells.
Effects of dexamethasone (DEX) on receptor binding of bovine PTH (1-34) [bPTH (1-34)] and human PTH-related protein (1-34) [hPTHrP(1-34)] and cAMP accumulation, and on the inhibition of Na(+)-dependent phosphate uptake were studied in opossum kidney (OK) cells. Maximal specific binding of [125I]hPTHrP(1-34) was reduced by 40% in cells treated with 100 nM DEX, but half-maximal inhibition of binding of [125I]hPTHrP(1-34) by bPTH(1-34) or hPTHrP(1-34) was unaffected by DEX (0.5 nM and 1.4 nM, in the absence and presence of DEX, respectively). Moreover, the EC50 of bPTH(1-34) and hPTHrP(1-34)-evoked cAMP accumulation ranged from 3-7 nM and was the same with and without DEX. The EC50 of the inhibition of phosphate uptake by bPTH(1-34) and hPTHrP(1-34) ranged from 0.2-0.5 nM. Treatment with 100 nM DEX increased phosphate uptake 1.5-fold (EC50 3 nM), and the inhibition of phosphate uptake by bPTH(1-34) and hPTHrP(1-34) was suppressed. The inhibition of phosphate uptake by forskolin was also suppressed in cells treated with 100 nM DEX. DEX, on the other hand, enhanced forskolin-stimulated cAMP accumulation 1.6- to 1.8-fold. 12-O-Tetradecanoylphorbol-13-acetate did not affect cAMP production, but phosphate uptake was inhibited both in the absence and the presence of 100 nM DEX (EC50 3 nM). In conclusion, treatment of OK cells with DEX only minimally affected PTH receptor binding, and cAMP accumulation evoked by bPTH(1-34) and hPTHrP(1-34) remained unaltered. The inhibition of phosphate uptake by PTH, however, was suppressed.
Kaufmann
M
M
Department of Orthopedic Surgery, University of Zurich, Switzerland.
Muff
R
R
Fischer
J A
JA
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone; D012964:Sodium / Q000494:pharmacology; D019379:Teriparatide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010703:Phorbol Esters; D010710:Phosphates; D011506:Proteins; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); C025076:parathyroid hormone (1-34), bovine; D005576:Colforsin; C008876:phorbol-12,13-didecanoate; D003907:Dexamethasone; D012964:Sodium; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate