Linked Life Data

9351968

Source:http://linkedlifedata.com/resource/pubmed/id/9351968

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-11-24
pubmed:abstractText
Although processes involved in mRNA degradation play a significant role in dictating steady state mRNA levels, the influence of cell surface signaling on mRNA stability control is understood incompletely. In this study, the effects of cAMP-elevating agents on type I angiotensin II receptor (AT1-R) mRNA levels were assessed in cultured rat aortic vascular smooth muscle cells (VSMCs). AT1-R mRNA levels are rapidly reduced by forskolin treatment, in which the maximal effect yields an 80% reduction in AT1-R mRNA levels after 6 hr of treatment. The rate of AT1-R mRNA decay in response to forskolin is greater than its apparent intrinsic decay, as assessed in the presence of the transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, suggesting forskolin treatment destabilizes the AT1-R mRNA. Nuclear run-on analysis indicates forskolin treatment does not affect transcription of the AT1-R gene in VSMCs, implying induced AT1-R mRNA destabilization accounts for the entire effect of forskolin in decreasing AT1-R mRNA levels. Dose-effect studies that assessed AT1-R mRNA levels and cAMP production were conducted using forskolin and the beta-adrenergic receptor agonist isoproterenol as agonists. Isoproterenol is almost 3 orders of magnitude more potent at eliciting the reduction in AT1-receptor mRNA levels than it is at stimulating cAMP production. Similarly, forskolin elicits reductions in AT1-R mRNA, which occur at concentrations that fail to elicit a detectable production of cAMP. However, protein kinase A activity is stimulated maximally by isoproterenol and forskolin concentrations that do not stimulate detectable cAMP production. These data provide evidence that the mechanism for down-regulation of AT1-R mRNA levels by cAMP-elevating agents in VSMCs occurs via a PKA-regulated mRNA destabilization pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
781-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
The vascular smooth muscle type I angiotensin II receptor mRNA is destabilized by cyclic AMP-elevating agents.
pubmed:affiliation
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't