Parathyroid hormone (PTH)-(1-34), [Nle(8,18),Tyr34]PTH-(3-34) amide, PTH-(1-31) amide, and PTH-related peptide-(1-34) stimulate phosphatidylcholine hydrolysis in UMR-106 osteoblastic cells: comparison with effects of phorbol 12,13-dibutyrate.
Studies were performed to determine the effects of PTH and related compounds on phosphatidylcholine (PC) hydrolysis in UMR-106 cells and the pathway by which the PTH effects occurred. The responses were compared with those of phorbol 12,13-dibutyrate (PDBu). Both bovine PTH-(1-34) [bPTH-(1-34)] and PDBu stimulated PC hydrolysis within 10 min. Significant effects were elicited by concentrations of 0.3-1 nM bPTH-(1-34) and 5 nM PDBu. Dose-dependent increases were seen at higher concentrations of both compounds, however, the response to bPTH-(1-34) was reduced at 30 nM. Bovine or human PTH-(1-34) and human PTH-related peptide-(1-34) [hPTHrP-(1-34)] were equipotent in their effects, whereas bovine [Nle(8,18)Tyr34]PTH-(3-34) amide [bPTH-(3-34)] and hPTH-(1-31) amide [hPTH-(1-31)] were less potent than bPTH-(1-34). bPTH-(3-34) did not antagonize the effects of bPTH-(1-34). Down-regulation of protein kinase C isozymes by 24-h treatment with PDBu completely prevented the stimulatory effect of PDBu on PC hydrolysis, but did not significantly affect the stimulatory effect of bPTH-(1-34). Both bPTH-(1-34) and PDBu stimulated transphosphatidylation of PC, indicating a phospholipase D-stimulated mechanism. The results suggest that in the UMR-106 cell line PTH can stimulate activation of PLD by a mechanism other than through protein kinase C.
Singh
A T
AT
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA. a-singh@nwu.edu
Kunnel
J G
JG
Strieleman
P J
PJ
Stern
P H
PH
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006728:Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D010006:Osteoblasts / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000008:administration & dosage / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D006728:Hormones; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); C025076:parathyroid hormone (1-34), bovine; C102836:parathyroid hormone (1-31)amide, human; D015240:Phorbol 12,13-Dibutyrate; C025497:parathyroid hormone (3-34) amide, Nle(8,18)-Nle(34)-; D011493:Protein Kinase C; D010739:Phospholipase D