From platelet membrane

Thrombin, thromboxane A2 and exposed collagen cause release of arachidonic acid from platelet membrane. 

Human-platelet membranes have been extracted with lithium 3,5-diiodosalicylate, and the soluble glycoproteins separated on O-phosphonocellulose.849 The purified, membrane glycoprotein, molecular weight 100,000, was immunochemically identical to a sample purified from platelet-membrane extract by means of con A-Sepharose affinity chromatography. No further characterization was reported,... 

Painter RG, PRODOUZ KN, GAARDE W. isolation of a sul x ulation of glycoprotein llbllla from platelet membranes that is bound to memlx ane actia JCdl Biol 100 652-657,1985. 

Quinton TM, Dean WL cydic AMP-dependent phosphorylation of the inositol-1.4.5-tris[4iosphate recephar inhibits Ca release from platelet membranes. Biochem Biophys Commun 184 893-899 1 2. 

The enzymatic pathways that are responsible for the initial mobilization of AA (20 4, 0)-6) as well as other PUFAs for eicosanoid thesis, are being discussed in detail in chapter 13 of this book. Once the AA (20 4, w-6) is released from platelet membrane phospholipids, it is rapidly metabolized via the cyclooxygenase and lipoxygenase... 

Thromboxane syn esis in platelets is triggered by the release of AA from platelet membrane phospholipids (14). This initial release appears to occur through activation of two major pathways a) the first pathway involves a sequoitial hydrolysis of 1, 2-diacylglycerol (DAG) fcxmed during platelet receptm -coupled activatirm of phospholipase C/D (PLC/PLD), by DAG- and monoacylglycerol (MAG) lipases, re )ectivefy (21,22). We have shown that hydrolysis of DAG by this pathwty results equimolar amounts of saturated fat acids (stearic palmitic acids) fixxn the sn-1 position and unsaturated fatty acids [oleic acid (18 1, -9), linoleic acid (18 2, co-6) and... 

While the data suggested that subtyping of Gc derived from bloodstains was feasible, one problem remained to be solved. Actin readily complexes with Gc causing an anodal shift of the Gc bands (44-53). The actin is released from platelet membranes when platelets lyse during bloodstain formation (49-53). The Gc-actin complex can be disrupted in the presence of urea (54 55). 

Selectins or their ligands may also self-associate in the plane of the membrane. PSGL-1 is a dimer, which may improve binding avidity by contributing recognition determinants from both subunits. Hydrodynamic analysis indicates that P-selectin isolated from platelet membranes is oligomeric even in nonionic detergent above... 

Isolated platelet phosphatides, especially the serine phosphoglycer-ide family, can replace the entire platelet in in vitro coagulation tests but the lipid itself is not as eiBcient as lipoprotein particles derived from platelet membranes or granules. Although the molar ratio of saturated to unsaturated fatty acids in platelet phosphatides is unity, there are large amounts of long-chain, highly unsaturated fatty acids present. 

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Lichtenberg- Kraag B, May T, Schmidt LG et al (1995) Changes of G-protein levels in platelet membranes from alcoholics during short-term and long-term abstinence. Alcohol Alcohol 30 455-464... 

Zubenko GS, Kopp U, Seto T, Firestone LL (1999) Platelet membrane fluidity individuals at risk for Alzheimer s disease a comparison of results from fluorescence spectroscopy and electron spin resonance spectroscopy. Psychopharmacology (Berl) 145(2) 175-180... 

Kotite, N.J., Staros, J.V., and Cunningham, L.W. (1984) Interaction of specific platelet membrane proteins with collagen Evidence from chemical cross-linking. Biochemistry 23, 3099-3104. 

To date, there have only been a limited number of studies directly examining PKC in bipolar disorders [77], Although undoubtedly an oversimplification, particulate (membrane) PKC is sometimes viewed as the more active form of PKC, and thus an examination of the subcellular partitioning of this enzyme can be used as an index of the degree of activation. Friedman etal. [78] investigated PKC activity and PKC translocation in response to serotonin in platelets obtained from bipolar-disorder patients before and during lithium treatment. They reported that the ratios of platelet-membrane-bound to cytosolic PKC activities were elevated in the manic patients. In addition, serotonin-elicited platelet PKC translocation was found to be enhanced in those patients. With respect to brain tissue, Wang and Friedman [74] measured PKC isozyme levels, activity and translocation in postmortem brain tissue from patients with bipolar disorder, and reported increased PKC activity and translocation in the brains of bipolar patients compared with controls, effects which were accompanied by elevated levels of selected PKC isozymes in cortices of bipolar disorder patients. 

A neolignan isolated by the Merck group from the plant Piperfutokadsurae, was the first natural product discovered as a potent inhibitor of the binding of [3H ]PAF to rabbit platelet membrane preparation with an IC50 close to 0.1 /iM [268]. Named kadsurenone (26), it was also shown to be a specific and potent inhibitor of PAF-induced rabbit platelet aggregation with an IC50 value of 0.99 juM. 

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. 

It has been hypothesized that depression could arise from a pathological enhancement of 5-HT2 receptor function. This view would concur with the observations that the functional activity of 5-HT2 receptors on the platelet membrane is enhanced in depression and the increase in the density of 5-HT2 receptors in the frontal cortex of brains from suicide victims. It is possible that enhanced 5-HT2 receptor function is associated primarily with anxiety, a common feature of depression, and that the increased activity of the 5-HT2 receptors results in an attenuation of the functioning of S-HT receptors thereby resulting in the symptoms of depression. Whether this change in the activity of S-HT receptors is due to direct effects of the altered 5-HT2 receptor function is uncertain. There is evidence that hypercortisolaemia, which is a characteristic feature of depression, reduces the activity of these receptors probably through central glucocorticoid type 2 receptors. Clearly further research is needed to determine the precise interaction between the 5-HT2 and 5-HTi receptor types. 

As the name implies, these drugs have a high affinity for the serotonin transporter both on neuronal and also platelet membranes. There is abundant evidence that the SSRIs inhibit the reuptake of 3H-5-HT into platelets, brain slices and synaptosomal fractions, as illustrated in Table 7.10, but it is clear that there is no direct relationship between the potency of the drug to inhibit 5-HT reuptake in vitro and the dose necessary to relieve depression in the clinic. In experimental studies, it is clear that the increased release of 5-HT from the frontal cortex only occurs following the chronic (2 weeks or longer) administration of any of the SSRIs. Thus the inhibition of 5-HT reuptake may be a necessary condition for the antidepressant activity, but it is not sufficient in itself. 

Figure 8.2 A developing blood clot is shown in this picture. A blood clot is made of platelets, membrane fragments of a bone marrow cell, and a network of insoluble proteins, particularly fibrin generated from a precursor protein, fibrinogen, through the work of a cascade of protein clotting factors. Several bleeding disorders result from inherited deficiencies in clotting proteins.

Lorenzo s oil affected blood platelet counts in 39 patients followed for 1 year (2). Blood platelet aggregation studies in those patients were normal and there were no platelet-associated immunoglobulins. It has been suggested that the thrombocytopenia might be due to platelet activation, resulting from an increase in the concentration of erucic acid in the platelet membrane (1). 

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