Linked Life Data

8864895

Source:http://linkedlifedata.com/resource/pubmed/id/8864895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1996-12-26
pubmed:abstractText
We studied the effects of parathyroid hormone (PTH) on PTH parathyroid hormone related peptide (PTHrP) receptor mRNA level, PTHrP binding and PTH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblasts, derived from fetal rat calvariae (ROB). Cells isolated during 10-70 minutes of collagenase treatment were seeded at a density of 25,000 cells/cm2 and cultured for 4 days. These cells show a fast increase in cAMP production after stimulation for 5 minutes with 20 nM bovine parathyroid hormone(1-34) (bPTH(1-34)). When ROB are incubated with bPTH(1-34) (0.04-40nM) for 24 h, a dose-dependent decrease of the PTH/PTHrP receptor mRNA level, PTHrP binding, and PTH-stimulated cAMP accumulation can be observed. Pretreatment of ROB with a high concentration of bPTH(1-34) (40 nM) leads within 15 minutes to a decrease in PTH-stimulated cAMP accumulation. However, it takes > or = 3 h before a significant decrease in PTH/PTHrP receptor mRNA level can be observed. Also a significant decrease in PTHrP binding is observed after only 4 h of incubation with bPTH(1-34). Compared with bPTH(1-34), pretreatment of ROB with bPTH(3-34) (40 and 100 nM) for 24 h causes smaller decreases in PTH-stimulated cAMP accumulation, PTHrP binding, and in the PTH/PTHrP receptor mRNA level. We investigated the possible involvement of the protein kinase A signaling pathway in the regulation of the PTH/PTHrP receptor mRNA expression. Both forskolin and (Bu)2cAMP decreased PTHrP binding and PTH/PTHrP mRNA levels. These observations suggest that chronic activation of the PKA signaling pathway may down-regulate PTH/PTHrP receptor expression and thus hormone responsiveness in "normal" osteoblasts. In short, we found that the decrease of the PTH-stimulated cAMP accumulation after long-term pretreatment with bPTH(1-34) is correlated with both PTH/PTHrP receptor mRNA level and PTHrP binding. These data also suggest that the initial desensitization (< 30 minutes) of PTH-stimulated cAMP responsiveness by pretreatment with a high concentration of bPTH(1-34) (40 nM) is not dependent on the number of available PTH/PTHrP receptors. The protein kinase A signaling pathway is involved in the regulation of the PTH/PTHrP receptor, but, regarding the effect of bPTH(3-34), other signaling systems are also involved.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0884-0431
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1218-25
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8864895-Animals, pubmed-meshheading:8864895-Blotting, Northern, pubmed-meshheading:8864895-Bucladesine, pubmed-meshheading:8864895-Cattle, pubmed-meshheading:8864895-Cell Count, pubmed-meshheading:8864895-Cells, Cultured, pubmed-meshheading:8864895-Cyclic AMP, pubmed-meshheading:8864895-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:8864895-Dose-Response Relationship, Drug, pubmed-meshheading:8864895-Down-Regulation, pubmed-meshheading:8864895-Forskolin, pubmed-meshheading:8864895-Osteoblasts, pubmed-meshheading:8864895-Parathyroid Hormone-Related Protein, pubmed-meshheading:8864895-Protein Binding, pubmed-meshheading:8864895-Proteins, pubmed-meshheading:8864895-Radioligand Assay, pubmed-meshheading:8864895-Rats, pubmed-meshheading:8864895-Receptors, Parathyroid Hormone, pubmed-meshheading:8864895-Signal Transduction, pubmed-meshheading:8864895-Teriparatide
pubmed:year
1996
pubmed:articleTitle
Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by PTH in primary fetal rat osteoblasts.
pubmed:affiliation
Laboratory of Cell Biology and Histology, University of Leiden, The Netherlands.
pubmed:publicationType
Journal Article