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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
36
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pubmed:dateCreated |
1989-1-24
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pubmed:abstractText |
Thrombin-stimulated endothelial cells produce platelet-activating factor (PAF) in a dose-dependent manner: the activation of a Ca2+-dependent lyso-PAF acetyltransferase is the rate-limiting step in this process. The present study shows that acetyltransferase activation and consequent PAF production induced by thrombin in human endothelial cells are markedly inhibited in Na+-free media or after addition of the amiloride analog 5-(N-ethyl-N-isopropyl)amiloride, suggesting that a Na+/H+ antiport system is present in endothelial cells and plays a prominent role in thrombin-induced PAF synthesis. Accordingly, thrombin elicits a sustained alkalinization in 6-carboxyfluorescein-loaded endothelial cells, that is abolished in either Na+-free or 5-(N-ethyl-N-isopropyl)amiloride-containing medium. Extracellular Ca2+ influx induced by thrombin (as measured by quin2 and 45Ca methods) is completely blocked in the same experimental conditions, and monensin, a Na+/H+ ionophore mimicking the effects of the antiporter activation, evokes a dose-dependent PAF synthesis and a marked Ca2+ influx, which are abolished in Ca2+-free medium. An amiloride-inhibitable Na+/H+ exchanger is present in the membrane of human endothelial cells, its apparent Km for extracellular Na+ is 25 mM, and its activity is greatly enhanced when the cytoplasm is acidified. These results suggest that Na+/H+ exchange activation by thrombin and the resulting intracellular alkalinization play a direct role in the induction of Ca2+ influx and PAF synthesis in human endothelial cells.
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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/Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Amiloride,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Monensin,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Activating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/ethylisopropylamiloride
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19437-46
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2848827-Acetyltransferases,
pubmed-meshheading:2848827-Amiloride,
pubmed-meshheading:2848827-Calcium,
pubmed-meshheading:2848827-Carrier Proteins,
pubmed-meshheading:2848827-Cells, Cultured,
pubmed-meshheading:2848827-Endothelium, Vascular,
pubmed-meshheading:2848827-Humans,
pubmed-meshheading:2848827-Hydrogen-Ion Concentration,
pubmed-meshheading:2848827-Kinetics,
pubmed-meshheading:2848827-Monensin,
pubmed-meshheading:2848827-Platelet Activating Factor,
pubmed-meshheading:2848827-Sodium-Hydrogen Antiporter,
pubmed-meshheading:2848827-Thrombin,
pubmed-meshheading:2848827-Umbilical Veins
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pubmed:year |
1988
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pubmed:articleTitle |
Role of Na+/H+ exchange in thrombin-induced platelet-activating factor production by human endothelial cells.
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pubmed:affiliation |
Department of Genetics, Biology, and Medical Chemistry, University of Torino, Italy.
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pubmed:publicationType |
Journal Article
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