Platelet plasma membrane, arachidonate

The choline- and ethanolamine-containing phospholipids of human platelets can be subdivided, based on the nature of the linkage to the fatty acid residue at the sn-1 position of the glycerol backbone, into 1,2-diacyl, l-O-alkyl-2-acyl and l-0-alk-l -enyl-2-acyl species (Table 1.2). The majority of arachidonic acid in the phosphatidylcholines is present in the diacyl species while 1-0-alk-l enyl-2-acyl-PE (plasmalogen) contains most of the arachidonic acid in the phosphatidylethanolamines. The amount of arachidonic acid present in the diacyl species of phosphatidylethanolamine is similar to that in diacyl phosphatidylcholine. Ferret et al have shown that the distribution of arachidonate in the phospholipids of the platelet plasma membrane is asymmetric, the majority of it being present in the inner leaflet. 

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

Prostacyclin, a potent inhibitor of platelet aggregation, is derived from metabo-lisation of arachidonic acid by endothelial cells, and shear stress increases its production rate [12]. It is postulated that this effect is due to perturbations of the permeability of the plasma membrane changing the cytosolic Ca + content and leading to an increase in phospholipase C activity (through the by-passing of the receptor requirement), which contributes to a higher production of arachidonic metabolites. 

FIGURE 9.98 Events taking place in the plasma membrane on stimulation of a cell. Phospha tidylinositol (Pi) and more hi ly phosphoiylated versions of this lipid account for 2 to 8% of the lipids of the plasma membrane of eukaryotic cdIs. The inositol 1,4,5 triphosphate (fP3) moiety of phosphatidyl inositol- 4,8-di phosphate may be hydiulyitec from this lipid immediately after the cell is stimulated. For example, the stimulation of platelets by thrombin or the islets of the pancreas by glucose is followed by the release of 1P3 into the cytoplasm. In some cells, arachidonic acid is hydrolyzed from l-acyl-2-arachidonyl-glyceroL which can Support a burst of prostaglandin. synthesis. 

Fig. 2.4 Diagram showing the effect of ischemic injury on glycerophospholipid-derived iipid mediators in brain. Plasma membrane (PM) iV-methyl-D-aspartate receptor (NMDA-R) giuteimate (GIu) phosphatidylcholine (PtdCho) lyso-phosphatidylcholine (lyso-PtdCho) cytosolic phospholipase A2 (CPLA2) secretory phospholipase A2 (SPLA2) cyclooxygenase (COX-2) arachidonic add (ARA) platelet-activating factor (RAF) 4-hydroxynonenal (4-HNE) reactive oxygen species (ROS) nuclear factor kappaB (NF-kB) nuclear factor kappaB response element (NF-kB-RE) inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-ip (IL-ip) interleukin-6 (IL-6) matrix metaUoproteinases (MMPs) positive sign (+) represents upregulation...

No absolute fatty acid specificity has yet been demonstrated for platelet phospholipase A2. Thus, it is possible that the specificity of arachidonic acid release does not depend on the enzyme itself but rather the fact that the platelet contains specific arachidonate-enriched membrane domains, such as the inner plasma membrane, in which the l-acyl-2-arachidonoyl-phospholipids are located. 

Ferret, B., Chap, H.J. and Douste-Blazy, L. (1979). Asymmetric distribution of arachidonic acid in the plasma membrane of human platelets. A determination using purified phospholipases and a rapid method for membrane isolation. Biochim. Biophys. Acta, 556, 434-446... 

However, it has been shown that both coronary artery disease and the platelet and coagulation systems in swine are very similar to those in hunums, and that the clinical syndromes of sudden death and acute myocardial infarction appear to be comparable [63, 64, 122]. Recently, it was demonstrated that after dietary supplementation with cod-liver oil severely hyperlipidemic swine exhibit retarded atherosclerotic disease development, with no relation to changes in plasma lipids, but associated with changes in the arachidonate and eicosapentaenoic acid content of platelet membranes [123]. Moreover, cats fed with menhaden oil showed significantly smaller neurological deficits after ligation of the left middle cerebral artery [13], and dogs fed with cod-liver oil exhibited smaller sizes of infarcted myocardial tissue than controls after electrical stimulation of the left circumflex coronary artery [22]. 

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