Linked Life Data

11093787

Source:http://linkedlifedata.com/resource/pubmed/id/11093787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-12-27
pubmed:abstractText
We have investigated factors modulating expression of inducible NO synthase (iNOS) in isolated adult rat cardiac fibroblasts. Treatment of cardiac fibroblasts with interleukin-1beta (IL-1beta) promotes induction of iNOS mRNA and protein and production of NO. Simultaneous incubation of cells with isoproterenol enhances the response to IL-1beta, even though isoproterenol alone is without effect. N(G)-nitro-L-arginine methyl ester inhibits the effect of isoproterenol + IL-1beta on NO production. beta(2)-Adrenergic receptors appear to mediate this effect of isoproterenol. Reverse transcriptase-polymerase chain reaction analyses show that beta(2)-receptor mRNA is the predominant beta-receptor message; in pharmacologic studies, ICI-118,551 significantly antagonizes isoproterenol-stimulated cyclic AMP production whereas CGP20712A does not. Dibutyryl-cyclic AMP and forskolin mimic the synergistic effect of isoproterenol on IL-1beta-induced NO production; H-89, a cyclic AMP-dependent protein kinase (PKA) inhibitor, antagonizes the enhancing effect of isoproterenol. Nuclear run-off experiments indicate that enhancement of iNOS by isoproterenol does not occur at the level of transcription. Message stability studies demonstrate that isoproterenol increases the half-life of iNOS mRNA from 1.0 to 1.9 h; this change is sufficient to account for the observed augmentation of iNOS mRNA and protein. Thus, cardiac fibroblasts produce significant amounts of NO in response to IL-1beta via induction of iNOS; beta-adrenergic stimulation enhances the IL-1beta effect by stabilizing the iNOS message. These data suggest that cardiac fibroblasts could participate in a paracrine mechanism whereby the direct positive inotropic effect of beta(1)-adrenergic stimulation of myocytes is opposed by beta(2)-adrenergic enhancement of NO production, a negative inotropic event, in neighboring fibroblasts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1470-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
beta-adrenergic stimulation of rat cardiac fibroblasts enhances induction of nitric-oxide synthase by interleukin-1beta via message stabilization.
pubmed:affiliation
Biomedical Sciences Graduate Program, Departments of Pharmacology and Medicine, University of California at San Diego, La Jolla, California 92093-0636, USA. agustafsson@ucsd.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't