Linked Life Data

16171811

Source:http://linkedlifedata.com/resource/pubmed/id/16171811

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-10-24
pubmed:abstractText
Adrenergic receptors (ARs) play an important role in the regulation of cardiac function. Cardiac inotropy is primarily regulated by beta(1)-ARs. However, alpha(1)-ARs may play an important role in inotropy during heart failure. Previous work has suggested that the alpha(1B)-AR modulates beta(1)-AR function in the heart. The potential role of the alpha(1A)-AR has not been previously studied. We used transgenic mice that express constitutively active mutant (CAM) forms of the alpha(1A)-AR or alpha(1B)-AR regulated by their endogenous promoters. Expression of the CAM alpha(1A)-AR or CAM alpha(1B)-AR had no effect on basal cardiac function (developed pressure, +dP/dT, -dP/dT, heart rate, flow rate). However, both alpha(1)-AR subtypes significantly decreased isoproterenol-stimulated +dP/dT. Pertussis toxin had no effect on +dP/dT in CAM alpha(1A)-AR hearts but restored +dP/dT to non-transgenic values in CAM alpha(1B)-AR hearts. Radioligand binding indicated a selective decrease in the density of beta(1)-ARs in both CAM mice. However, G-proteins, cAMP, or the percentage of high and low affinity states were unchanged in either transgenic compared with control. These data demonstrate that CAM alpha(1A)- and alpha(1B)-ARs both down regulate beta(1)-AR-mediated inotropy in the mouse heart. However, alpha(1)-AR subtypes are coupled to different beta-AR mediated signaling pathways with the alpha(1B)-AR being pertussis toxin sensitive.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
777-84
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Both alpha(1A)- and alpha(1B)-adrenergic receptors crosstalk to down regulate beta(1)-ARs in mouse heart: coupling to differential PTX-sensitive pathways.
pubmed:affiliation
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, NB5, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural