Linked Life Data

1703603

Source:http://linkedlifedata.com/resource/pubmed/id/1703603

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-3-1
pubmed:abstractText
The involvement of rolipram-sensitive phosphodiesterase (PDE IV) in regulation of cardiac contraction was investigated by studying the effect of selective inhibitors (rolipram, denbufylline, Ro 20-1724) on guinea pig left atria contraction. In contrast to milrinone and SK&F 94120 (inhibitors of the cyclic GMP-inhibited PDE, PDE III), (+/-)-rolipram and denbufylline (0.1-30 microM) did not produce any positive inotropic effect in normal (2.5 mM) or elevated (3-3.2 mM) external CaCl2 concentration. In these conditions, Ro 20-1724 produced only a slight but significant increase of contraction over control levels. In the presence of forskolin (an adenylate cyclase activator) or SK&F 94120 (a PDE III inhibitor), which produced an increase of the response to electrical stimulation of approximately 10%, (+/-)-rolipram, denbufylline, and Ro 20-1724 all exerted concentration-dependent positive inotropic effects (mean EC50 values were 20, 25, and 125 nM, respectively, in the presence of forskolin). Rolipram exhibited stereospecificity: the (-)-enantiomer was 10 times more potent than the (+)-enantiomer. Neither preincubation of the atria with atenolol nor pretreatment of the guinea pigs with reserpine significantly modified the effect of PDE IV inhibitors obtained in the presence of forskolin. These data show that in the presence of cyclic AMP-dependent positive inotropic agents, PDE IV inhibitors exert a positive inotropic effect which probably does not involve enhanced catecholamine release from sympathetic nerve endings. This suggests that PDE IV may play a role in regulation of cardiac contraction in physiologic conditions in which the sympathetic outflow produces a stimulation of adenylate cyclase in cardiac cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3',5'-Cyclic-AMP Phosphodiesterases, http://linkedlifedata.com/resource/pubmed/chemical/4-(3-Butoxy-4-methoxybenzyl)-2-imida..., http://linkedlifedata.com/resource/pubmed/chemical/5-(4-acetamidophenyl)pyrazin-2(1H)-o..., http://linkedlifedata.com/resource/pubmed/chemical/Atenolol, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Chloride, http://linkedlifedata.com/resource/pubmed/chemical/Forskolin, http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidinones, http://linkedlifedata.com/resource/pubmed/chemical/Reserpine, http://linkedlifedata.com/resource/pubmed/chemical/Rolipram, http://linkedlifedata.com/resource/pubmed/chemical/Xanthines, http://linkedlifedata.com/resource/pubmed/chemical/denbufylline
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
796-803
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Involvement of rolipram-sensitive cyclic AMP phosphodiesterase in the regulation of cardiac contraction.
pubmed:affiliation
Laboratoire de Pharmacologie Cellulaire et Moléculaire, CNRS URA 600, Université Louis Pasteur de Strasbourg, Illkirch, France.
pubmed:publicationType
Journal Article, In Vitro