Linked Life Data

2423089

Source:http://linkedlifedata.com/resource/pubmed/id/2423089

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1986-6-18
pubmed:abstractText
Cyclic nucleotide phosphodiesterase (PDE) activity from the 105,000 g supernatant of human, bovine and rat aorta smooth muscle cells was resolved by DEAE-trisacryl chromatography into three major forms showing similar properties in each species. In addition to the two PDE forms previously characterized in vascular tissues (a cAMP-PDE and a calmodulin-dependent PDE), a cGMP-PDE, insensitive to calmodulin, was isolated and characterized in the aorta of the three species. Each isolated PDE form was differently inhibited by various chemical compounds, and these compounds produced effects on cyclic nucleotide levels in isolated rat aorta which could be expected from their inhibitory effect on isolated PDE forms. At concentrations non-selectively inhibiting the three isolated PDE forms (including the calmodulin-dependent one), IBMX (3-isobutyl-1-methylxanthine) and trequinsin markedly and dose-dependently increased both cAMP and cGMP aorta levels (up to 7-fold, in presence of 500 microM IBMX). By contrast selective inhibitors of cGMP-PDE or cAMP-PDE could only induce a moderate elevation (by 1.5-3-fold) in cGMP or cAMP levels, respectively. In the case of M&B 22,948, a highly specific and potent inhibitor of cGMP-PDE, a concentration-dependent increase in tissue cGMP levels was produced by concentrations (in the microM range) active in inhibiting the isolated enzyme. In the case of selective cAMP-PDE inhibitors (rolipram and Ro 20-1724), however, a significant increase in aorta cAMP content was induced only in the presence of drug concentrations which were much higher (200 and 500 microM, respectively) than those inhibiting the isolated enzyme (IC50:5 and 18 microM, respectively). Inhibitors of both cGMP-PDE and cAMP-PDE (dipyridamole, cilostamide and its derivative AAL 05) produced the same moderate effects as did the combination of a selective cGMP-PDE inhibitor and a selective cAMP-PDE inhibitor on the levels of both cGMP and cAMP. These results show that the three forms of PDE isolated from aortic smooth muscle retain properties that they exhibit in the tissue and which are similar in the three species examined, including man. They suggest that each form participates in a specific manner to the regulation of cAMP and cGMP concentrations in aorta smooth muscle cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1743-51
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:2423089-1-Methyl-3-isobutylxanthine, pubmed-meshheading:2423089-2',3'-Cyclic-Nucleotide Phosphodiesterases, pubmed-meshheading:2423089-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:2423089-3',5'-Cyclic-GMP Phosphodiesterases, pubmed-meshheading:2423089-Animals, pubmed-meshheading:2423089-Aorta, pubmed-meshheading:2423089-Cattle, pubmed-meshheading:2423089-Cyclic AMP, pubmed-meshheading:2423089-Cyclic GMP, pubmed-meshheading:2423089-Cyclic Nucleotide Phosphodiesterases, Type 1, pubmed-meshheading:2423089-Humans, pubmed-meshheading:2423089-Kinetics, pubmed-meshheading:2423089-Muscle, Smooth, Vascular, pubmed-meshheading:2423089-Purinones, pubmed-meshheading:2423089-Rats, pubmed-meshheading:2423089-Species Specificity, pubmed-meshheading:2423089-Substrate Specificity
pubmed:year
1986
pubmed:articleTitle
Selective inhibition of cyclic nucleotide phosphodiesterases of human, bovine and rat aorta.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't