rdf:type |
|
lifeskim:mentions |
umls-concept:C0031621,
umls-concept:C0300926,
umls-concept:C0330390,
umls-concept:C0441655,
umls-concept:C0596235,
umls-concept:C0597298,
umls-concept:C1152760,
umls-concept:C1514762,
umls-concept:C1552644,
umls-concept:C1554184,
umls-concept:C1823153,
umls-concept:C2349976
|
pubmed:issue |
2
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pubmed:dateCreated |
2008-1-11
|
pubmed:abstractText |
During thrombus formation, thrombin, which is abundantly present at sites of vascular injury, activates platelets in part via autocrine-produced ADP. We investigated the signaling pathways by which thrombin and ADP in synergy induced platelet Ca(2+) elevation and procoagulant activity, and we monitored the consequences for the coagulation process. Even at high thrombin concentration, autocrine and added ADP enhanced and prolonged Ca(2+) depletion from internal stores via stimulation of the P2Y(12) receptors. This P2Y(12)-dependent effect was mediated via two distinct signaling pathways. The first is enhanced Ca(2+) mobilization by the inositol 1,4,5-trisphosphate receptors due to inhibition of protein kinase A. The second pathway concerns prolonged activation of phosphoinositide 3-kinase (PI3-K) and phospholipase C. Experiments with phosphoinositide 3-kinase isoform-selective inhibitors and p110gamma deficient platelets demonstrated that the phosphoinositide 3-kinase beta and not the phosphoinositide 3-kinase gamma isoform is responsible for the prolonged Ca(2+) response and for the subsequent increases in procoagulant activity and coagulation. Taken together, these results demonstrate a dual P2Y(12)-dependent signaling mechanism, which increases the platelet-activating effect of thrombin by prolongation of Ca(2+) elevation, thereby facilitating the coagulation process.
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pubmed:commentsCorrections |
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Coagulants,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/P2RY12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2Y12,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin
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pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
1742-464X
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:volume |
275
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
371-85
|
pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18081863-Blood Platelets,
pubmed-meshheading:18081863-Calcium,
pubmed-meshheading:18081863-Coagulants,
pubmed-meshheading:18081863-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:18081863-Flow Cytometry,
pubmed-meshheading:18081863-Humans,
pubmed-meshheading:18081863-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:18081863-Isoenzymes,
pubmed-meshheading:18081863-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18081863-Receptors, Purinergic P2,
pubmed-meshheading:18081863-Receptors, Purinergic P2Y12,
pubmed-meshheading:18081863-Signal Transduction,
pubmed-meshheading:18081863-Thrombin
|
pubmed:year |
2008
|
pubmed:articleTitle |
Dual P2Y 12 receptor signaling in thrombin-stimulated platelets--involvement of phosphoinositide 3-kinase beta but not gamma isoform in Ca2+ mobilization and procoagulant activity.
|
pubmed:affiliation |
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, the Netherlands.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|