Linked Life Data

8569706

Source:http://linkedlifedata.com/resource/pubmed/id/8569706

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-3-1
pubmed:abstractText
Thrombin receptor activation, by thrombin or SFLLR-containing peptides, stimulates GTPase activity in platelet and CHRF-288 membranes. Polyclonal antibodies to peptides derived from the thrombin receptor (anti-TR52-69 and anti-TR36-49), which block many of thrombin's actions on platelets and endothelial cells, also block thrombin activation of membrane GTPase (as does thrombin active site and anion-binding exosite inhibitors). Most of the receptor-activated GTPase, stimulated by both thrombin and SFLLRNP in platelet membranes, was inhibited by prior treatment with pertussis toxin or N-ethylmaleimide, suggesting that under these conditions much of the thrombin receptor-stimulated GTPase in platelet membranes is a member of the pertussis toxin-sensitive G alpha i family. In platelet membrane preparations, the peptide agonists stimulated approximately twice as much GTPase activity as stimulated by alpha-thrombin. In contrast, the membranes prepared from CHRF-288 cells showed similar maximal SFLLRNP- and alpha-thrombin-stimulated GTPase activity. Stimulation of the platelet membrane GTPase by a variety of different peptide agonists correlated with their ability to stimulate platelet aggregation. Several peptide-based agonists were more potent than the wild-type sequence. The most potent was Ser-(p-fluoro-Phe)-(2-Napthyl-Ala)-Leu-Arg-NH2, which stimulated platelet aggregation (EC50 = 80 nM) and GTPase activity (EC50 = 110 nM). The peptide YFLLRN stimulated GTPase activity but only to approximately 40% of the activity observed with optimal concentrations of other receptor agonists. YFLLRN also limited the stimulation observed with SFLLRNP in a competitive fashion, indicating that YFLLRN is a competitive partial agonist at the thrombin receptor. These studies show that the tethered-ligand receptor mediates the GTPase activation by thrombin in platelet and CHRF-288 cell membranes, and this provides a specific, reliable, and convenient cell-free assay system with which one can evaluate agonists and partial agonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
190-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Thrombin receptor activation by thrombin and receptor-derived peptides in platelet and CHRF-288 cell membranes: receptor-stimulated GTPase and evaluation of agonists and partial agonists.
pubmed:affiliation
Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.
pubmed:publicationType
Journal Article