Source:http://linkedlifedata.com/resource/pubmed/id/11160856
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
YC-1 is a direct activator of soluble guanylyl cyclase (sGC) and sensitizes the enzyme for activation by nitric oxide (NO) and CO. Because the potentiating effect of YC-1 on NO-induced cGMP formation in platelets and smooth muscle cells has been shown to be substantially higher than observed with the purified enzyme, the synergism between heme ligands and YC-1 is apparently more pronounced in intact cells than in cell-free systems. Here, we investigated the mechanisms underlying the synergistic activation of sGC by YC-1 and NO in endothelial cells. Stimulation of the cells with YC-1 enhanced cGMP accumulation up to approximately 100-fold. The maximal effect of YC-1 was more pronounced than that of the NO donor DEA/NO (approximately 20-fold increase in cGMP accumulation) and markedly diminished in the presence of L-N(G)-nitroarginine, EGTA, or oxyhemoglobin. Because YC-1 did not activate endothelial NO synthase, the pronounced effect of YC-1 on cGMP accumulation was apparently caused by a synergistic activation of sGC by YC-1 and basal NO. The effect of YC-1 was further enhanced by addition of DEA/NO, resulting in a approximately 160-fold stimulation of cGMP accumulation. Thus, YC-1 increased the NO-induced accumulation of cGMP in intact cells by approximately 8-fold. Addition of endothelial cell homogenate increased the stimulatory effect of YC-1 on NO-activated purified sGC from 1.2- to 3.7-fold. This effect was not observed with heat-denatured homogenates, suggesting that a heat-labile factor present in endothelial cells potentiates the effect of YC-1 on NO-activated sGC.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(5'-hydroxymethyl-2'-furyl)-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Indazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
59
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
220-4
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11160856-Animals,
pubmed-meshheading:11160856-Cells, Cultured,
pubmed-meshheading:11160856-Cyclic GMP,
pubmed-meshheading:11160856-Drug Synergism,
pubmed-meshheading:11160856-Endothelium, Vascular,
pubmed-meshheading:11160856-Enzyme Activation,
pubmed-meshheading:11160856-Enzyme Activators,
pubmed-meshheading:11160856-Enzyme Inhibitors,
pubmed-meshheading:11160856-Guanylate Cyclase,
pubmed-meshheading:11160856-Indazoles,
pubmed-meshheading:11160856-Nitric Oxide,
pubmed-meshheading:11160856-Nitric Oxide Donors,
pubmed-meshheading:11160856-Nitric Oxide Synthase,
pubmed-meshheading:11160856-Swine
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pubmed:year |
2001
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pubmed:articleTitle |
Molecular mechanisms involved in the synergistic activation of soluble guanylyl cyclase by YC-1 and nitric oxide in endothelial cells.
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pubmed:affiliation |
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Graz, Austria. kurt.schmidt@kfunigraz.ac.at
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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