Source:http://linkedlifedata.com/resource/pubmed/id/12631586
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2003-3-12
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| pubmed:abstractText |
The role of Galpha(i)-2 overexpression in desensitization of beta-adrenergic signaling in heart failure is controversial. An adenovirus-based approach was used to investigate whether overexpression of Galpha(i)-2 impairs beta-adrenergic stimulation of adenylyl cyclase (AC) activity and cAMP levels in neonatal rat cardiac myocytes (NRCM) and cell shortening of adult rat ventricular myocytes (ARVM). Infection of NRCM with Ad5Galpha(i)-2 increased Galpha(i)-2 by 50-600% in a virus dose-dependent manner. Overexpression was paralleled by suppression of GTP- and isoprenaline-stimulated AC by 10-72% (P<0.001) in a PTX-sensitive manner. Isoprenaline-stimulated shortening of Ad5Galpha(i)-2-infected ARVM was attenuated by 34% (P<0.01). Ad5Galpha(i)-2/GFP (Galpha(i)-2, green fluorescent protein; bicistronic) was constructed to monitor transfection homogeneity and target Galpha(i)-2 overexpression to levels found in heart failure. At Galpha(i)-2 levels of 93% above control, isoprenaline-stimulated AC activity and cAMP levels were reduced by 17% and 40% (P<0.02), respectively. Beta1- and beta2-adrenergic stimulation was reduced similarly. Our results suggest that (a) the Galpha(i)-2 system exhibits tonic inhibition of stimulated AC in cardiac myocytes, (b) Galpha(i)-2-mediated inhibition is concentration-dependent and occurs at Galpha(i)-2 levels seen in heart failure, and (c) Galpha(i)-2-mediated inhibition affects both beta1- and beta2-adrenergic stimulation of AC. The data argue for an important, independent role of the Galpha(i)-2 increase in heart failure.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
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 Protein alpha Subunit...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Gnai2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
17
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
523-5
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12631586-Adenoviridae,
pubmed-meshheading:12631586-Adenylate Cyclase,
pubmed-meshheading:12631586-Adrenergic beta-Agonists,
pubmed-meshheading:12631586-Animals,
pubmed-meshheading:12631586-Cells, Cultured,
pubmed-meshheading:12631586-Cyclic AMP,
pubmed-meshheading:12631586-GTP-Binding Protein alpha Subunit, Gi2,
pubmed-meshheading:12631586-GTP-Binding Protein alpha Subunits, Gi-Go,
pubmed-meshheading:12631586-Gene Expression,
pubmed-meshheading:12631586-Genetic Vectors,
pubmed-meshheading:12631586-Isoproterenol,
pubmed-meshheading:12631586-Models, Biological,
pubmed-meshheading:12631586-Myocytes, Cardiac,
pubmed-meshheading:12631586-Pertussis Toxin,
pubmed-meshheading:12631586-Proto-Oncogene Proteins,
pubmed-meshheading:12631586-Rats,
pubmed-meshheading:12631586-Signal Transduction
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| pubmed:year |
2003
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| pubmed:articleTitle |
Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes.
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| pubmed:affiliation |
Institute of Pharmacology and Toxicology, Friedrich Alexander University Erlangen, Germany.
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| pubmed:publicationType |
Journal Article
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