Linked Life Data

11705454

Source:http://linkedlifedata.com/resource/pubmed/id/11705454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-11-13
pubmed:abstractText
We determined the effect of long-term exposure to beta-agonists on beta(1)-adrenergic receptors (beta(1)-AR) in human neuroepithelioma SK-N-MC cells because earlier studies have indicated that beta(1)-AR in this cell line are resistant to agonist-induced down-regulation. Exposing SK-N-MC cells to isoproterenol for 24 hr reduced the density of beta(1)-AR by 72%, whereas forskolin, an activator of all the isoforms of adenylyl cyclase, failed to affect the density of beta(1)-AR. Measurement of beta(1)-AR mRNA levels by the ribonuclease protection assay revealed that isoproterenol-induced down-regulation of beta(1)-AR was associated with a sharp decline in beta(1)-AR mRNA, while forskolin also failed to affect this parameter. The differences between the effects of isoproterenol and forskolin on beta(1)-AR were unrelated to cyclic AMP levels, since both agents increased cyclic AMP equally. Next, we determined the role of cyclic AMP-dependent protein kinase A (PKA) in this phenomenon. Inhibition of PKA by its specific inhibitor, H-89 [N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, 2HCl], markedly reduced the magnitude of the isoproterenol-mediated down-regulation of the beta(1)-AR and its mRNA. Transient expression of the catalytic subunit of PKA in SK-N-MC cells down-regulated beta(1)-AR independently of isoproterenol. Therefore, PKA is central to the effect of beta-agonists in down-regulating beta(1)-AR, and its spatial compartmentalization and access to the receptor appear to be essential components of its action.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1211-20
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Regulation of human beta(1)-adrenergic receptors and their mRNA in neuroepithelioma SK-N-MC cells: effects of agonist, forskolin, and protein kinase A.
pubmed:affiliation
Department of Pharmacology and Pharmaceutical Sciences, Colleges of Medicine and Pharmacy, The University of Tennessee Health Sciences Center, Memphis, TN 38163, USA. sbahouth@utmem.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't