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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1997-3-18
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pubmed:abstractText |
The effects of the imidazole compound SK&F 96365 on Ca2+ movements and production of nitric oxide (NO) and von Willebrand factor (vWF) have been investigated in human endothelial cells. Changes in cytosolic Ca2+ concentration ([Ca2+]i) were measured with Fura-2. Real-time production of NO was monitored with a porphyrinic microsensor and the release of vWF with an enzyme-linked immunosorbent assay. Irrespective of the transmembrane Ca2+ gradient, 30 microM SK&F 96365 doubled [Ca2+]i suggesting a Ca2+ release from intracellular stores. The SK&F 96365-induced [Ca2+]i rise was not accompanied by detectable NO and vWF production, while 1 microM thapsigargin enhanced [Ca2+]i 2.5 times, doubled the secretion of vWF and increased the NO production to 10 +/- 4 nM (n = 5). Pretreatment with SK&F 96365 prevented thapsigargin from increasing [Ca2+]i, NO production and vWF secretion. To investigate the mechanism by which SK&F 96365 released Ca2+ from internal pools, its effect and that of thapsigargin on the ATP-dependent 45Ca2+ uptake into platelet membrane vesicles were compared. SK&F 96365 as thapsigargin, dose-dependently reduced the initial rate of 45Ca2+ uptake. In conclusion, we demonstrate that, in the absence of Ca2+ entry from the extracellular space, the [Ca2+]i increase elicited by SK&F 96365 or thapsigargin is not sufficient to initiate NO synthesis and vWF secretion. This confirms the important role of Ca2+ influx in endothelial secretion processes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(2-(3-(4-methoxyphenyl)propoxy)-4-...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0143-4160
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
501-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:8985595-Adenosine Triphosphate,
pubmed-meshheading:8985595-Biological Transport,
pubmed-meshheading:8985595-Blood Platelets,
pubmed-meshheading:8985595-Calcium,
pubmed-meshheading:8985595-Calcium Channel Blockers,
pubmed-meshheading:8985595-Calcium Radioisotopes,
pubmed-meshheading:8985595-Calcium-Transporting ATPases,
pubmed-meshheading:8985595-Cells, Cultured,
pubmed-meshheading:8985595-Cytoplasm,
pubmed-meshheading:8985595-Dose-Response Relationship, Drug,
pubmed-meshheading:8985595-Enzyme Inhibitors,
pubmed-meshheading:8985595-Epithelial Cells,
pubmed-meshheading:8985595-Epithelium,
pubmed-meshheading:8985595-Humans,
pubmed-meshheading:8985595-Imidazoles,
pubmed-meshheading:8985595-Intracellular Membranes,
pubmed-meshheading:8985595-Nitric Oxide,
pubmed-meshheading:8985595-Thapsigargin,
pubmed-meshheading:8985595-Umbilical Veins,
pubmed-meshheading:8985595-von Willebrand Factor
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pubmed:year |
1996
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pubmed:articleTitle |
SK&F 96365 inhibits intracellular Ca2+ pumps and raises cytosolic Ca2+ concentration without production of nitric oxide and von Willebrand factor.
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pubmed:affiliation |
Department of Pharmacology, URA CNRS 1482, Necker University School of Medicine, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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