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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-10-1
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1241-9
pubmed:dateRevised
2009-11-19
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
pubmed:year
2003
pubmed:articleTitle
Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium.
pubmed:affiliation
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung für Pharmakologie, Universitätsklinikum Hamburg, Eppendorf Martinistrasse 52, 20246 Hamburg, Germany. mittmann@bfarm.de
pubmed:publicationType
Journal Article