Linked Life Data

15452191

Source:http://linkedlifedata.com/resource/pubmed/id/15452191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-16
pubmed:abstractText
Plasma adenosine levels are elevated in cardiovascular disease including hypertension and heart failure, and the nucleoside has been proposed to serve as an endogenous antimyocardial remodeling factor. We studied the modulation of phenylephrine-induced hypertrophy by adenosine receptor activation in isolated neonatal cultured ventricular myocytes. Phenylephrine (10 muM) increased cell size by 35% and significantly increased expression of atrial natriuretic peptide. These effects were reduced by the stable adenosine analog 2-chloroadenosine and were completely blocked by the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (1 microM), the A(2A) receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (100 nM), and the A(3) receptor agonist N(6)-(3-iodobenzyl)adenosine-5'-methyluronamide (100 nM). The antihypertrophic effects of all three agonists were completely reversed by their respective antagonists. Phenylephrine significantly up-regulated expression of the immediate early gene c-fos especially within the first 30 min of phenylephrine treatment. These effects were almost completely inhibited by all adenosine receptor agonists. Although phenylephrine also induced early stimulation of both p38 mitogen-activated protein kinase and extracellular signal-regulated kinase, these responses were unaffected by adenosine agonists. The expression of the G-protein regulatory factors RGS2 and RGS4 were increased by nearly 3-fold by phenylephrine treatment although this was completely prevented by adenosine receptor agonists. These agents also blocked the ability of phenylephrine to up-regulate Na/H exchange isoform 1 (NHE1) expression in hypertrophied myocytes. Thus, our results demonstrate an antihypertrophic effect of adenosine acting via multiple receptor subtypes through a mechanism involving down-regulation of NHE1 expression. The ability to prevent regulators of G-protein signaling (RGS) up-regulation further suggests that adenosine receptor activation minimizes signaling which leads to hypertrophic responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-(2-carboxyethyl)phenethylamino)..., http://linkedlifedata.com/resource/pubmed/chemical/Adenosine, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A1 Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A2 Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine A3 Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/N(6)-(3-iodobenzyl)-5'-N-methylcarbo..., http://linkedlifedata.com/resource/pubmed/chemical/N(6)-cyclopentyladenosine, http://linkedlifedata.com/resource/pubmed/chemical/Phenethylamines, http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A1, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A2A, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Adenosine A3
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
312
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-34
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes.
pubmed:affiliation
Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, London, Ontario N6A 5C1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't