Source:http://linkedlifedata.com/resource/pubmed/id/14519434
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2003-10-1
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pubmed:abstractText |
Muscarinic acetylcholine receptors (mAChRs) mediate their main cardiac effects via pertussis toxin-sensitive G-proteins. Physiological effects differ considerably between atrium and ventricle, and it is unknown to which extent these differences derive from selective receptor-G-protein coupling or further downstream events. We have characterized specific coupling between mAChRs and Gi/Go-protein isoforms in atrial and ventricular myocardium by agonist-dependent photoaffinity labeling with [(32)P]azidoanilido GTP (aaGTP) and immunoprecipitation in sarcolemmal membranes from terminally failing human hearts. The total amount of mAChRs, as determined by specific binding of [(3)H]QNB, was significantly higher in right-atrial (RA +/- SEM, 959 +/- 68 fmol/mg, n = 4) than in left-ventricular membranes (LV, 582 +/- 53 fmol/mg, n = 6). Standardized immunoblots revealed that Gialpha-2 was the predominant subtype in both regions. A 40-kDa splice variant of Goalpha (Goalpha-1 and/or Goalpha-3) was almost exclusively detectable in RA. Levels of Gialpha-3 and a 39-kDa splice variant of Goalpha (Goalpha-2) were also higher in RA. Basal aaGTP binding was higher in RA than in LV for all Gialpha/Goalpha subtypes. The carbachol (10 micromol/l)-induced increase in aaGTP binding was significantly higher in RA than in LV for Goalpha-1/3 (336 +/- 95% of LV, n = 4) and for Gialpha-3 (211 +/- 83%), lower for Gialpha-2 (42 +/- 5%), and was similar in both regions for Goalpha-2 (130 +/- 62%). The differential coupling of mAChRs in human RA and LV suggests that the initiation of different physiological responses to mAChR stimulation starts with signal sorting at the receptor-G-protein level.
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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/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2828
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1241-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14519434-Acetylcholine,
pubmed-meshheading:14519434-Adenosine Diphosphate,
pubmed-meshheading:14519434-Adenosine Diphosphate Ribose,
pubmed-meshheading:14519434-Adult,
pubmed-meshheading:14519434-Carbachol,
pubmed-meshheading:14519434-Cell Membrane,
pubmed-meshheading:14519434-Dose-Response Relationship, Drug,
pubmed-meshheading:14519434-Female,
pubmed-meshheading:14519434-GTP-Binding Protein alpha Subunits, Gi-Go,
pubmed-meshheading:14519434-Guanosine Triphosphate,
pubmed-meshheading:14519434-Humans,
pubmed-meshheading:14519434-Immunoblotting,
pubmed-meshheading:14519434-Light,
pubmed-meshheading:14519434-Male,
pubmed-meshheading:14519434-Middle Aged,
pubmed-meshheading:14519434-Myocardium,
pubmed-meshheading:14519434-Pertussis Toxin,
pubmed-meshheading:14519434-Precipitin Tests,
pubmed-meshheading:14519434-RNA, Messenger,
pubmed-meshheading:14519434-Receptors, Muscarinic,
pubmed-meshheading:14519434-Time Factors,
pubmed-meshheading:14519434-Tissue Distribution
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pubmed:year |
2003
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pubmed:articleTitle |
Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium.
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pubmed:affiliation |
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung für Pharmakologie, Universitätsklinikum Hamburg, Eppendorf Martinistrasse 52, 20246 Hamburg, Germany. mittmann@bfarm.de
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pubmed:publicationType |
Journal Article
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