Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-10-17
pubmed:abstractText
A cardiac phosphodiesterase (PDE) which specifically hydrolyzes cAMP and is inhibited by cyclic GMP has been suggested to be the site of action of new cardiotonic drugs. To investigate the effect of inhibitors, canine cyclic nucleotide PDEs were isolated from left ventricle and from sinoatrial node-enriched tissue, using identical techniques. Four PDE forms could be chromatographically resolved from each tissue, including a peak I PDE (calmodulin-activated phosphodiesterase, CaM-PDE), a peak II PDE (cyclic GMP-stimulated phosphodiesterase, CGS-PDE) and a peak III PDE (specific for cyclic AMP). The latter was further fractionated into two forms: One was inhibited by cyclic GMP and by the platelet antiaggregant AAL 05 (CGI-PDE), and the second was insensitive to cyclic GMP and was inhibited by rolipram (ROI-PDE). Reference PDE inhibitors, isobutyl-1-methylxanthine (IBMX) and papaverine, nonselectively inhibited the four forms isolated from the two tissues. Cardiotonic drugs (CI 930, LY 181512, piroximone, enoximone, and SK&F 94120) selectively inhibited CGI-PDE from ventricular tissue but were poorly active on both CGI-PDE and ROI-PDE from the sinoatrial-enriched fraction. In contrast, milrinone inhibited CGI-PDEs and ROI-PDEs from both ventricular and sinoatrial tissues. These results are in good agreement with pharmacologic data in the literature on the positive chronotropic and inotropic effects of the studied drugs in the dog. They provide a possible basis for the dissociation of these two properties of PDE inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-20
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Differential sensitivity to cardiotonic drugs of cyclic AMP phosphodiesterases isolated from canine ventricular and sinoatrial-enriched tissues.
pubmed:affiliation
Laboratoire de Pharmacologie Cellulaire et Moléculaire, CNRS UA 600, Université Louis Pasteur de Strasbourg, Toulouse, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't