Linked Life Data

14602550

Source:http://linkedlifedata.com/resource/pubmed/id/14602550

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-6
pubmed:abstractText
Selective activation of the platelet TXA2 receptor is sufficient to mediate concurrent aggregation, deaggregation and shape change (SC) responses without activation of known Gi-coupled receptors (Platelets 2003; 14: 89). However, Gi-coupled receptor activation strongly influences the hemostasis response in vivo. This study investigated the modulatory effects of two signaling pathways related to Gi-coupled receptor activation, stimulation of phosphoinositide 3-kinases (PI3Ks) and inhibition of adenylyl cyclase (AC), on the aggregation, deaggregation and SC components of the platelet activation response. A novel turbidimetric approach was applied to separate these responses and to characterize their pharmacology and kinetics. The SC response was more sensitive to TXA2 receptor activation (lower EC50 value) but less sensitive to a TXA2 receptor antagonist (higher Kd value) than the net aggregation response. Epinephrine and sulprostone, agonists of the Gi-coupled alpha2A-adrenoceptor and EP3 receptor, respectively, amplified the SC, decelerated deaggregation and enhanced net aggregation responses. SQ22536 and 2',5'-dideoxyadenosine, inhibitors of AC activity, elicited smaller but qualitatively similar effects. The PI3K inhibitor wortmannin did not affect the SC response but accelerated deaggregation and inhibited net aggregation. These data are consistent with a differential modulation of the platelet SC response by each pathway associated with Gi-coupled receptor activation, while both pathways cooperatively enhance the net aggregation response by decelerating deaggregation. We propose that the TXA2 receptor mediated concurrent platelet aggregation and SC responses, that are differentially modulated by different signaling pathways, provide a model for studying the underlying cellular pharmacology of platelet physiology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0953-7104
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
359-74
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Diversity of signaling underlying responses mediated by selective activation of the platelet thromboxane A2 (TXA2) receptor; pharmacological and kinetic studies in vitro.
pubmed:affiliation
Department of Anesthesiology, The Mount Sinai School of Medicine, New York, NY 10029, USA. saul.maayani@mssm.edu
pubmed:publicationType
Journal Article