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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5 Pt 1
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pubmed:dateCreated |
1997-7-8
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pubmed:abstractText |
Chronic catecholamine treatment induces beta-adrenergic receptor (beta AR) downregulation, i.e., a loss of total cell receptors. In the human respiratory tract, the mechanism(s) underlying beta AR downregulation remains poorly understood. The present study, therefore, examined the effects of 24 h of exposure to isoproterenol (Iso; 10 nM or 1 microM) on beta AR density and the rate of beta AR degradation, steady-state beta 2-adrenergic receptor (beta 2 AR) mRNA levels, and the content of Gs alpha and Gi alpha proteins in cultured human bronchial epithelial cells (i.e., the BEAS-2B cell line). beta AR density assessed by binding with [125I]iodopindolol decreased in a dose-dependent fashion with 24 h of Iso exposure. With Iso (1 microM), beta AR density decreased by approximately 82%. In contrast, forskolin (100 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM), agents that also increase adenosine 3',5'-cyclic monophosphate (cAMP) levels, had no significant effect on beta AR density. Iso exposure also elicited a concomitant decrease in Iso-stimulated cAMP but had no significant effect on the content of the G proteins G alpha i2 and Gs alpha assessed by immunoblotting and toxin-catalyzed ADP ribosylation. Of note, Iso exposure (1 microM) had no effect on steady-state levels of beta 2 AR mRNA measured both by Northern analysis and by reverse transcriptase-polymerase chain reaction. However, beta AR half-life assessed in the presence of the protein synthesis inhibitor cycloheximide was reduced by approximately 60% in Iso-treated cells (i.e., from 37 h in control to 16 h in 1 microM Iso). These results suggest that, in human airway epithelial cells, beta 2 AR downregulation 1) is not primarily driven by intracellular cAMP levels, 2) is not associated with significant decreases in steady-state levels of beta 2 AR mRNA, and 3) is largely posttranslationally regulated by increases in the rate of receptor protein degradation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
L916-24
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9176257-Adrenergic beta-Agonists,
pubmed-meshheading:9176257-Bronchi,
pubmed-meshheading:9176257-Cell Line,
pubmed-meshheading:9176257-Cyclic AMP,
pubmed-meshheading:9176257-Down-Regulation,
pubmed-meshheading:9176257-Epithelial Cells,
pubmed-meshheading:9176257-Epithelium,
pubmed-meshheading:9176257-GTP-Binding Proteins,
pubmed-meshheading:9176257-Humans,
pubmed-meshheading:9176257-Isoproterenol,
pubmed-meshheading:9176257-RNA, Messenger,
pubmed-meshheading:9176257-Receptors, Adrenergic, beta,
pubmed-meshheading:9176257-Time Factors
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pubmed:year |
1997
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pubmed:articleTitle |
Chronic effects of catecholamines on the beta 2-adrenoreceptor system in cultured human airway epithelial cells.
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pubmed:affiliation |
Department of Medicine, Temple University School of Medicine, Philadelphia 19140, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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