Platelet activation mechanism

Dr. Douglas J. Weiss is a Professor at the College of Veterinary Medicine at the UrMversity of Minnesota. Over the years, he has been extensively involved in both teaching and research at the College. He has received a number of awards for his teaching. His research interests include platelet activation mechanisms in thrombotic diseases, mechanisms of acute lung injury and mucosal inflammation. He has published extensively on his research. 

Platelets play a central role in primary hemostasis. They are also important in pathological processes leading to thrombosis. Antiplatelet drugs are primarily directed against platelets and inhibit platelet activation by a number of different mechanisms. They are used for the prevention and treatment of thrombotic processes, especially in the arterial vascular system. 

Kroll MH, Schafer Al Biochemical mechanisms of platelet activation. Blood 1989 74 1181. 

The mechanisms involved in platelet activation are discussed in Chapter 51 (see Figure 51-8). The process involves interaction of the stimulus (eg, thrombin) with a receptor, activation of G proteins, stimulation of phospholipase C, and hberation from phosphatidylinositol... 

Fig. 9.1. A dysfunctional or injured endothelium is at the basis for initiation of and progression to atherosclerosis. Several mechanisms, such as adhesion molecules or liberation of von Willebrand factor (vWf, upper panel), determine a series of phenomena, including platelet activation and aggregation. This participation of platelets involves the implication of molecules like glycoprotein Ilb/IIIa, fibrinogen, and von Willebrand factor. The endothelium also acts as a source of signals that regulate local functions, including VSMCs (lower panel). A list of the most relevant messengers produced by a functional and a dysfunctonal endothelium is presented in the lower panel...

Inhibition of platelet activation by NO is not exclusively cGM P-dependent but involves mechanisms independent of cGM P like ribosylation or nitrosylation of proteins. For... 

DETA/NO is a stable NO-donor with the longest NO generation half-life of approximately 20 h. Thrombelastography performed on rabbit blood showed that DETA NONOate-derived NO significantly decreased coagulation activity and platelet activation [48]. Monitoring by intravital microscopy showed that DETA/NO attenuated the platelets/endothelial cells adhesion response to endotoxins (e.g. lipopolysaccharides) in murine intestinal venules [49]. The main mechanism of the antiadhesive action of DETA/NO on platelets was activation of soluble guanylate cyclase [49]. 

Chapter 7 outlines the basic mechanism and treatment of emesis, and in particular, that induced by chemotherapy of cancer. Finally, the chemistry, pharmacology and clinical applications of antagonists of the platelet-activating factor (PAF), an important mediator of many physiological and pathological conditions, are reviewed in Chapter 8. 

Unlike iNOS and nNOS, the eNOS protein is post-translationally modified by the attachment of fatty acids, myristate or palmitate. This modification is important because the fatty acids help to attach the enzyme, in an inactive form, to the inner face of plasma membrane of endothelial cells or platelets. Several mechanisms serve to release eNOS from its membrane bound state and thus activate the enzyme. 

Vascular and hematologic effects Ginkgo exerts vascular effects through at least two mechanisms inhibition of platelet-activating factor (PAF) and nitric oxide mechanisms. Ginkgo extract relaxes the porcine basilar artery in a concentration-dependent and partly endothelium-dependent manner (Chen et al. 1997). It also enhances vasorelaxation created by transmural nerve stimulation in arteries with and without the endothelium intact, and is prevented by nitro-L-arginine, indicating that the effect is mediated by nitric oxide. 

The pathogenesis of TTP is complex, and possibly involves a variety of mechanisms associated with endothelial cell and platelet activation and injury. Recently, however, the deficiency of vWF cleaving prolease aclivily has been idenlified as a hallmark of TTP (67, 68). In normal individuals, vWF is secreted from platelets and endothelial cells as variously sized multimers, resulting from the crosslinking of vWF monomers by disulfide bonds into multimers containing a minimum of 2 to a maximum of 50-100 monomer subunits. 

It has beat proposed that possible mechanisms underlying the neuroprotective and/or neurotrophic properties of EGb in the CNS indude influences on neurotransmitters, energy metabolism and membrane functions, as well as antioxidant activities and inhibition of platelet-activation factor (PAF). 

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