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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1989-6-16
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pubmed:abstractText |
We have investigated the effects of endothelin on phosphoinositide metabolism and Ca2+ mobilization in cultured A10 cells. Endothelin stimulated a significant increase in inositol phosphate formation in a time- and dose-dependent manner. IP3 was significantly elevated by 30 sec and reached a 2.0-fold above control at 1 min. The EC50 for endothelin was 0.5 nM. The initiation of inositol phosphate formation was independent of extracellular Ca2+, and the Ca2+ ionophore, A23187, did not stimulate IP3 formation. However, the sustained elevation of inositol phosphates was partially inhibited by incubating cells in buffer lacking Ca2+ or in buffer containing nicardipine. Endothelin mobilized both intracellular and extracellular Ca2+ reaching a peak intracellular concentration of 350 +/- 11 nM by 1 min when cells were bathed with Ca2+-complete buffer. Intracellular Ca2+ remained 2-fold above baseline for at least 15 min. In contrast, when cells were exposed to endothelin in Ca2+-free buffer, the peak value of [Ca2+]i was 195 +/- 20 nM and returned to baseline by 2 min. Nicardipine completely blocked the influx of extracellular Ca2+ but did not interfere with the mobilization of intracellular stores. We conclude that endothelin produces a rapid and sustained elevation in inositol phosphate formation. The rapid production of IP3 is consistent with the time course for mobilization of intracellular Ca2+. Elevated cytosolic Ca2+ levels are maintained by the influx of extracellular Ca2+ through a nicardipine-sensitive Ca2+ channel and are involved in the sustained formation of inositol phosphates. These data provide an explanation for the sustained, nicardipine-inhibitable contraction of coronary artery strips induced by endothelin.
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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/1,4-dihydropyridine,
http://linkedlifedata.com/resource/pubmed/chemical/Benzofurans,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Nicardipine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Sugar Phosphates
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
160
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
758-64
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:2541709-Animals,
pubmed-meshheading:2541709-Benzofurans,
pubmed-meshheading:2541709-Calcium Channels,
pubmed-meshheading:2541709-Cell Line,
pubmed-meshheading:2541709-Dihydropyridines,
pubmed-meshheading:2541709-Endothelins,
pubmed-meshheading:2541709-Endothelium, Vascular,
pubmed-meshheading:2541709-Fluorescent Dyes,
pubmed-meshheading:2541709-Fura-2,
pubmed-meshheading:2541709-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:2541709-Inositol Phosphates,
pubmed-meshheading:2541709-Kinetics,
pubmed-meshheading:2541709-Muscle, Smooth, Vascular,
pubmed-meshheading:2541709-Nicardipine,
pubmed-meshheading:2541709-Peptides,
pubmed-meshheading:2541709-Phosphatidylinositol 4,5-Diphosphate,
pubmed-meshheading:2541709-Phosphatidylinositols,
pubmed-meshheading:2541709-Rats,
pubmed-meshheading:2541709-Sugar Phosphates
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pubmed:year |
1989
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pubmed:articleTitle |
Inhibition by nicardipine of endothelin-mediated inositol phosphate formation and Ca2+ mobilization in smooth muscle cell.
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pubmed:affiliation |
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710.
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pubmed:publicationType |
Journal Article
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