Linked Life Data

1667833

Source:http://linkedlifedata.com/resource/pubmed/id/1667833

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-7-2
pubmed:abstractText
When a blood vessel is disrupted, subendothelial structures such as collagen come into contact with circulating blood platelets. These will adhere and recruit additional platelets to form a platelet aggregate which will close the leak, but which can, under certain circumstances, give rise to the formation of a thrombus. In this work our personal contribution to a better understanding of this process is given. We could demonstrate the presence of an antibody interfering with the platelet-collagen interaction in two patients with a bleeding problem. One of the antibodies is directed against glycoprotein (GP) Ia, a known collagen receptor, the other one recognizes a less well characterized protein of 85-90 kD. It therefore can be concluded that activation of blood platelets requires the simultaneous interaction of collagen with multiple receptors. Activation of platelets following binding of an agonist in many instances involves activation of phospholipase C via a GTP-binding protein or G-protein. We have further studied this by using a direct stimulator of G-proteins, AlF4-, which in platelets indeed activates phospholipase C, together with other systems. Furthermore, we could demonstrate that activation of phospholipase C in a GTP-dependent manner also occurs in platelet cytosol, indicating that the action of G-proteins is not restricted to membrane-linked phenomena. Activation of phospholipase C gives rise to the formation of inositol phosphates, of which mainly inositol 1, 4, 5 trisphosphate increases intracellular Ca(2+)-levels. Following this, the Ca(2+)-dependent phospholipase A2 releases arachidonic acid from the membranes. In platelets arachidonic acid is metabolised to another platelet activator: thromboxane A2. We have studied the effects of the inhibition of this aggregation-amplifying pathway by using specific inhibitors of the synthesis of thromboxane A2 and of thromboxane A2 receptor antagonists both in vitro and in vivo. One of the conclusions that were reached from these studies was that theoretically the combination of these two classes of drugs should yield a significant stronger antiplatelet effect than either class used alone. We could later on confirm this hypothesis, which stimulated some pharmaceutical companies to look for dual action compounds, of which we have studied two so far.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:language
dut
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0302-6469
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-604
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
[Signal transduction in blood platelets].
pubmed:affiliation
Centrum voor Trombose en Vasculair Onderzoek, K.U. Leuven.
pubmed:publicationType
Journal Article, English Abstract, Review