Linked Life Data

12132038

Source:http://linkedlifedata.com/resource/pubmed/id/12132038

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-10-18
pubmed:abstractText
Studies from our laboratory in osteoblast-like cells have shown that the increase in EGF receptor expression in response to PTH was cyclic AMP mediated and was blocked by treatment with retinoic acid (RA). The present studies investigate the mechanism for this effect of RA on PTH actions. UMR 106-01 cells were exposed to RA and were tested for cAMP response to PTH as well as for (125)I PTH binding. cAMP production in response to PTH was markedly decreased by RA (25.1 +/- 1.6% of control) whereas there was only a slight decrease in PTH binding in response to RA. For the study of adenylate cyclase activity, membranes were isolated from intact cells that had been exposed to RA. Treatment with RA decreased PTH-stimulated adenylate cyclase activity; however, forskolin-stimulated enzyme activity was unchanged. Treatment of intact cells with pertussis toxin, to inactivate Gi, did not alter the inhibitory effect of RA on PTH-stimulated adenylate cyclase activity. Addition of GppNHp, a non-hydrolyzable analogue of GTP, completely restored the response to PTH in the membranes. Therefore, we examined the activity of IMP dehydrogenase, the rate-limiting enzyme for GTP biosynthesis, and GMP reductase which counteracts the effect of the synthetic enzyme. Treatment with RA for 48 hours increased GMP reductase activity by 240.9 +/- 24.2% and decreased IMP dehydrogenase activity to 67.5 +/- 8.8% of control values. These data indicate that RA impairs the response to PTH in intact cells. This blunted response was preserved in membrane preparations but was corrected by GTP. The RA-induced alterations of enzymes involved in the GTP biosynthetic pathway in a direction that favors a decrease in GTP biosynthesis provide an explanation for the inhibitory effect of RA on PTH actions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0171-967X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12132038-Adenylate Cyclase, pubmed-meshheading:12132038-Animals, pubmed-meshheading:12132038-Binding Sites, pubmed-meshheading:12132038-Cell Line, pubmed-meshheading:12132038-Cell Membrane, pubmed-meshheading:12132038-Cyclic AMP, pubmed-meshheading:12132038-Dose-Response Relationship, Drug, pubmed-meshheading:12132038-Drug Antagonism, pubmed-meshheading:12132038-Forskolin, pubmed-meshheading:12132038-GMP Reductase, pubmed-meshheading:12132038-Guanylyl Imidodiphosphate, pubmed-meshheading:12132038-IMP Dehydrogenase, pubmed-meshheading:12132038-NADH, NADPH Oxidoreductases, pubmed-meshheading:12132038-Osteoblasts, pubmed-meshheading:12132038-Parathyroid Hormone, pubmed-meshheading:12132038-Pertussis Toxin, pubmed-meshheading:12132038-Rats, pubmed-meshheading:12132038-Tretinoin
pubmed:year
2002
pubmed:articleTitle
Mechanism of retinoic acid induced attenuation of PTH action in UMR 106-01 cells.
pubmed:affiliation
Division of Nephrology, Saint Louis University, St. Louis, Missouri 63110, USA. gonzalea@slu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.